Size-dependent forced PEG partitioning into channels: VDAC, OmpC, and α-hemolysin

DOE PAGES

Aksoyoglu, M. Alphan; Podgornik, Rudolf; Bezrukov, Sergey M.; ...

2016-07-27

Nonideal polymer mixtures of PEGs of different molecular weights partition differently into nanosize protein channels. Here, we assess the validity of the recently proposed theoretical approach of forced partitioning for three structurally different beta-barrel channels: voltage-dependent anion channel from outer mitochondrial membrane VDAC, bacterial porin OmpC (outer membrane protein C), and bacterial channel-forming toxin alpha-hemolysin. Our interpretation is based on the idea that relatively less-penetrating polymers push the more easily penetrating ones into nanosize channels in excess of their bath concentration. Comparison of the theory with experiments is excellent for VDAC. Polymer partitioning data for the other two channels aremore » consistent with theory if additional assumptions regarding the energy penalty of pore penetration are included. In conclusion, the obtained results demonstrate that the general concept of "polymers pushing polymers" is helpful in understanding and quantification of concrete examples of size-dependent forced partitioning of polymers into protein nanopores.« less

Size-dependent forced PEG partitioning into channels: VDAC, OmpC, and α-hemolysin

PubMed Central

Aksoyoglu, M. Alphan; Podgornik, Rudolf; Bezrukov, Sergey M.; Gurnev, Philip A.; Muthukumar, Murugappan; Parsegian, V. Adrian

2016-01-01

Nonideal polymer mixtures of PEGs of different molecular weights partition differently into nanosize protein channels. Here, we assess the validity of the recently proposed theoretical approach of forced partitioning for three structurally different β-barrel channels: voltage-dependent anion channel from outer mitochondrial membrane VDAC, bacterial porin OmpC (outer membrane protein C), and bacterial channel-forming toxin α-hemolysin. Our interpretation is based on the idea that relatively less-penetrating polymers push the more easily penetrating ones into nanosize channels in excess of their bath concentration. Comparison of the theory with experiments is excellent for VDAC. Polymer partitioning data for the other two channels are consistent with theory if additional assumptions regarding the energy penalty of pore penetration are included. The obtained results demonstrate that the general concept of “polymers pushing polymers” is helpful in understanding and quantification of concrete examples of size-dependent forced partitioning of polymers into protein nanopores. PMID:27466408

The host outer membrane proteins OmpA and OmpC are associated with the Shigella phage Sf6 virion

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

Zhao Haiyan, E-mail: zhaohy@ku.ed; Sequeira, Reuben D., E-mail: sequen@ku.ed; Galeva, Nadezhda A., E-mail: galeva@ku.ed

2011-01-20

Assembly of dsDNA bacteriophage is a precisely programmed process. Potential roles of host cell components in phage assembly haven't been well understood. It was previously reported that two unidentified proteins were present in bacteriophage Sf6 virion (Casjens et al, 2004, J.Mol.Biol. 339, 379-394, Fig. 2A). Using tandem mass spectrometry, we have identified the two proteins as outer membrane proteins (OMPs) OmpA and OmpC from its host Shigella flexneri. The transmission electron cryo-microscopy structure of Sf6 shows significant density at specific sites at the phage capsid inner surface. This density fit well with the characteristic beta-barrel domains of OMPs, thus maymore » be due to the two host proteins. Locations of this density suggest a role in Sf6 morphogenesis reminiscent of phage-encoded cementing proteins. These data indicate a new, OMP-related phage:host linkage, adding to previous knowledge that some lambdoid bacteriophage genomes contain OmpC-like genes that express phage-encoded porins in the lysogenic state.« less

Genetic improvement of butanol tolerance in Escherichia coli by cell surface expression of fish metallothionein.

PubMed

Lin, Kuo Hsing; Chin, Wei Chih; Lee, Ang Hsuan; Huang, Chieh Chen

2011-01-01

Cysteine-rich metallothioneins (MTs) have been reported to possess the capacity to scavenge reactive oxygen species in vitro and in vivo. Recombinant strains of Escherichia coli expressing outer membrane protein C (OmpC) fused with MTs from human, mouse and tilapia displayed the ability for such surface-localized MTs to scavenge extracellular free radicals, but the benefits of the possible applications of this capacity have not yet been demonstrated. Because the intrinsic butanol tolerance of microbes has become an impediment for biological butanol production, we examined whether surface-displayed MTs could contribute to butanol tolerance. The results show that strains expressing OmpC-MT fusion proteins had higher butanol tolerance than strains with cytoplasmically expressed MTs. Furthermore, the OmpC-tilapia MT fusion protein enhanced butanol tolerance more strongly than other recombinant constructs. Although the enhanced level of tolerance was not as high as that provided by OmpC-tilapia MT, over-expression of OmpC was also found to contribute to butanol tolerance. These results suggest that free-radical scavenging by MT and OmpC-related osmoregulation enhance butanol tolerance. Our results shed new light on methods for engineering bacteria with higher butanol tolerance. © 2011 Landes Bioscience

Cytokines and growth factors which regulate bone cell function

NASA Astrophysics Data System (ADS)

Seino, Yoshiki

Everybody knows that growth factors are most important in making bone. Hormones enhance bone formation from a long distance. Growth factors promote bone formation as an autocrine or paracrine factor in nearby bone. BMP-2 through BMP-8 are in the TGF-β family. BMP makes bone by enchondral ossification. In bone, IGF-II is most abundant, second, TGF-β, and third IGF-I. TGF-β enhances bone formation mainly by intramembranous ossification in vivo. TGF-β affects both cell proliferation and differentiation, however, TGF-β mainly enhances bone formation by intramembranous ossification. Interestingly, TGF-β is increased by estrogen(E 2), androgen, vitamin D, TGF-β and FGF. IGF-I and IGF-II also enhance bone formation. At present it remains unclear why IGF-I is more active in bone formation than IGF-II, although IGF-II is more abundant in bone compared to IGF-I. However, if only type I receptor signal transduction promotes bone formation, the strong activity of IGF-I in bone formation is understandable. GH, PTH and E 2 promotes IGF-I production. Recent data suggest that hormones containing vitamin D or E 2 enhance bone formation through growth factors. Therefore, growth factors are the key to clarifying the mechanism of bone formation.

Subcutaneous administration of insulin-like growth factor (IGF)-II/IGF binding protein-2 complex stimulates bone formation and prevents loss of bone mineral density in a rat model of disuse osteoporosis

NASA Technical Reports Server (NTRS)

Conover, Cheryl A.; Johnstone, Edward W.; Turner, Russell T.; Evans, Glenda L.; John Ballard, F. John; Doran, Patrick M.; Khosla, Sundeep

2002-01-01

Elevated serum levels of insulin-like growth factor binding protein-2 (IGFBP-2) and a precursor form of IGF-II are associated with marked increases in bone formation and skeletal mass in patients with hepatitis C-associated osteosclerosis. In vitro studies indicate that IGF-II in complex with IGFBP-2 has high affinity for bone matrix and is able to stimulate osteoblast proliferation. The purpose of this study was to determine the ability of the IGF-II/IGFBP-2 complex to increase bone mass in vivo. Osteopenia of the femur was induced by unilateral sciatic neurectomy in rats. At the time of surgery, 14-day osmotic minipumps containing vehicle or 2 microg IGF-II+9 microg IGFBP-2/100g body weight/day were implanted subcutaneously in the neck. Bone mineral density (BMD) measurements were taken the day of surgery and 14 days later using a PIXImus small animal densitometer. Neurectomy of the right hindlimb resulted in a 9% decrease in right femur BMD (P<0.05 vs. baseline). This loss in BMD was completely prevented by treatment with IGF-II/IGFBP-2. On the control limb, there was no loss of BMD over the 14 days and IGF-II/IGFBP-2 treatment resulted in a 9% increase in left femur BMD (P<0.05). Bone histomorphometry indicated increases in endocortical and cancellous bone formation rates and in trabecular thickness. These results demonstrate that short-term administration of the IGF-II/IGFBP-2 complex can prevent loss of BMD associated with disuse osteoporosis and stimulate bone formation in adult rats. Furthermore, they provide proof of concept for a novel anabolic approach to increasing bone mass in humans with osteoporosis.

Influence of bone morphogenetic protein and proportion of hydroxyapatite on new bone formation in biphasic calcium phosphate graft: two pilot studies in animal bony defect model.

PubMed

Yun, Pil-Young; Kim, Young-Kyun; Jeong, Kyung-In; Park, Ju-Cheol; Choi, Yeon-Jo

2014-12-01

The purpose of these two pilot studies using animal bony defect models was to evaluate the influence of bone morphogenetic protein (BMP) and proportion of hydroxyapatite (HA)/beta-tricalcium phosphate (β-TCP) in biphasic calcium phosphate (BCP) graft on new bone formation. In this study, four kinds of synthetic osteoconductive bone materials known for bone growth scaffold, OSTEON™II(HA:β-TCP 30:70), OSTEON™III (HA:β-TCP 20:80), OSTEON™II Collagen, and OSTEON™III Collagen, were prepared as BCP graft materials. In pilot study 1, three BCP materials (OSTEON™II, OSTEON™III, and OSTEON™II Collagen) were grafted in rabbit calvarial defects after impregnating in rhBMP-2. OSTEON™II without the rhBMP-2 impregnation was included in the study as the control. The amount of new bone was examined and measured histologically at 2, 4, and 8 weeks. In pilot study 2, four BCP materials (OSTEON™II, OSTEON™III, OSTEON™II Collagen, and OSTEON™III Collagen) were grafted in beagle dog mandibular defects after soaking in the rhBMP-2. The amount of total bone and new bone were measured three-dimensionally using microCT and healing process was examined histologically at 2, 4, and 8 weeks. In pilot study 1, rhBMP-2 impregnated groups showed more new bone formation than the rhBMP-2 free group. In pilot study 2, increased new bone formation was observed in time-dependent manner after graft of BCP and BCP-collagen (OSTEON™II, OSTEON™III, OSTEON™II Collagen, and OSTEON™III Collagen) impregnated with rhBMP-2. Also, BCP with a higher proportion of HA (30% HA) showed more favorable result in new bone formation and space maintenance, especially at the 8 weeks. From the results of the pilot studies, rhBMP-2 played positive roles in new bone formation and BCP could become a scaffold candidate for rhBMP-2 impregnation to induce new bone formation. Moreover, BCP with a higher proportion of HA (30% HA) could be considered more appropriate for rhBMP-2 carrier. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Tolerance to MHC class II disparate allografts through genetic modification of bone marrow

PubMed Central

Jindra, Peter T.; Tripathi, Sudipta; Tian, Chaorui; Iacomini, John; Bagley, Jessamyn

2012-01-01

Induction of molecular chimerism through genetic modification of bone marrow is a powerful tool for the induction of tolerance. Here we demonstrate for the first time that expression of an allogeneic MHC class II gene in autologous bone marrow cells, resulting in a state of molecular chimerism, induces tolerance to MHC class II mismatched skin grafts, a stringent test of transplant tolerance. Reconstitution of recipients with syngeneic bone marrow transduced with retrovirus encoding H-2I-Ab (I-Ab) resulted the long-term expression of the retroviral gene product on the surface of MHC class II-expressing bone marrow derived cell types. Mechanistically, tolerance was maintained by the presence of regulatory T cells, which prevented proliferation and cytokine production by alloreactive host T cells. Thus, the introduction of MHC class II genes into bone marrow derived cells through genetic engineering results in tolerance. These results have the potential to extend the clinical applicability of molecular chimerism for tolerance induction. PMID:22833118

The influence of implant design on periprosthetic bone remodelling of two types of uncemented HA-coated hip stems. A two-year follow-up study using DEXA.

PubMed

Van der Wal, B C H; Rahmy, A I A; Grimm, B; Blake, G M; Heyligers, I C; Tonino, A J

2006-01-01

Proximal bone resorption and an increased fracture rate in the ABG-I stem has been shown. For these reasons the ABG-I stem design was changed to the ABG-II. In this study periprosthetic bone loss around the ABG-I vs ABG-II is compared to verify if the design changes resulted in improved proximal bone preservation. 51 patients were randomised to either the ABG-I or ABG-II hip prosthesis. Periprosthetic BMD change at various time points was measured using DEXA. Between the two groups (age, gender, weight etc.) no statistical difference was encountered. Compared to the baseline at two years the ABG-II preserved bone better proximally (e.g. zone 7: ABG-II: -3.7%, ABG-I: -11.9%, p=0.05) than the ABG-I. Distally, the trend was opposite and less bone loss was measured for the ABG-I than the ABG-II in zones 3, 4 and 5 (n.s.). this study confirms the philosophy behind the design changes from the ABG-I to ABG-II stem where increased elasticity, more proximal HA-coating, a shorter and distally polished stem, were meant to reduce proximal bone resorption. In future this may lead to fewer periprosthetic fractures and to less complicated revision surgery.

Improvement of n-butanol tolerance in Escherichia coli by membrane-targeted tilapia metallothionein

PubMed Central

2013-01-01

Background Though n-butanol has been proposed as a potential transportation biofuel, its toxicity often causes oxidative stress in the host microorganism and is considered one of the bottlenecks preventing its efficient mass production. Results To relieve the oxidative stress in the host cell, metallothioneins (MTs), which are known as scavengers for reactive oxygen species (ROS), were engineered in E. coli hosts for both cytosolic and outer-membrane-targeted (osmoregulatory membrane protein OmpC fused) expression. Metallothioneins from human (HMT), mouse (MMT), and tilapia fish (TMT) were tested. The host strain expressing membrane-targeted TMT showed the greatest ability to reduce oxidative stresses induced by n-butanol, ethanol, furfural, hydroxymethylfurfural, and nickel. The same strain also allowed for an increased growth rate of recombinant E. coli under n-butanol stress. Further experiments indicated that the TMT-fused OmpC protein could not only function in ROS scavenging but also regulate either glycine betaine (GB) or glucose uptake via osmosis, and the dual functional fusion protein could contribute in an enhancement of the host microorganism’s growth rate. Conclusions The abilities of scavenging intracellular or extracellular ROS by these engineering E. coli were examined, and TMT show the best ability among three MTs. Additionally, the membrane-targeted fusion protein, OmpC-TMT, improved host tolerance up to 1.5% n-butanol above that of TMT which is only 1%. These results presented indicate potential novel approaches for engineering stress tolerant microorganism strains. PMID:24020941

Improvement of n-butanol tolerance in Escherichia coli by membrane-targeted tilapia metallothionein.

PubMed

Chin, Wei-Chih; Lin, Kuo-Hsing; Chang, Jui-Jen; Huang, Chieh-Chen

2013-09-11

Though n-butanol has been proposed as a potential transportation biofuel, its toxicity often causes oxidative stress in the host microorganism and is considered one of the bottlenecks preventing its efficient mass production. To relieve the oxidative stress in the host cell, metallothioneins (MTs), which are known as scavengers for reactive oxygen species (ROS), were engineered in E. coli hosts for both cytosolic and outer-membrane-targeted (osmoregulatory membrane protein OmpC fused) expression. Metallothioneins from human (HMT), mouse (MMT), and tilapia fish (TMT) were tested. The host strain expressing membrane-targeted TMT showed the greatest ability to reduce oxidative stresses induced by n-butanol, ethanol, furfural, hydroxymethylfurfural, and nickel. The same strain also allowed for an increased growth rate of recombinant E. coli under n-butanol stress. Further experiments indicated that the TMT-fused OmpC protein could not only function in ROS scavenging but also regulate either glycine betaine (GB) or glucose uptake via osmosis, and the dual functional fusion protein could contribute in an enhancement of the host microorganism's growth rate. The abilities of scavenging intracellular or extracellular ROS by these engineering E. coli were examined, and TMT show the best ability among three MTs. Additionally, the membrane-targeted fusion protein, OmpC-TMT, improved host tolerance up to 1.5% n-butanol above that of TMT which is only 1%. These results presented indicate potential novel approaches for engineering stress tolerant microorganism strains.

Pneumococcal Conjugate Vaccines and Otitis Media: An Appraisal of the Clinical Trials

PubMed Central

Fletcher, Mark A.; Fritzell, Bernard

2012-01-01

Streptococcus pneumoniae is the predominant otitis media pathogen and its prevention through effective vaccination could diminish childhood illness and antibiotic use. This paper reviews 5 pneumococcal conjugate vaccine (PCV) trials that used otitis media as an endpoint: Northern California Kaiser Permanente (NCKP; vaccine, 7-valent PCV [PCV7]-CRM); Finnish Otitis Media (FinOM; vaccines, PCV7-CRM or PCV7-OMPC); Native American Trial (vaccine, PCV7-CRM); Pneumococcal Otitis Efficacy Trial (POET; vaccine, 11-valent PCV [PCV11]-PD). For the microbiological endpoint, vaccine efficacy against vaccine-serotype pneumococcal otitis media was about 60% across trials. Against the clinical endpoint of all episodes, vaccine efficacy was 7% (PCV7-CRM/NCKP), 6% (PCV7-CRM/FinOM), −1% (PCV7-OMPC/FinOM), and −0.4% (PCV7-CRM/Native American Trial); 34% against first episodes of ear, nose, and throat specialist-referral cases (PCV11-PD/POET). Both follow-up through 2 years of age, for the 5 trials, and long-term follow-up, for PCV7-CRM/NCKP and PCV7-CRM/FinOM, demonstrated greater vaccine efficacy against recurrent AOM and tympanostomy-tube placement, suggesting that vaccination against early episodes of AOM may prevent subsequent episodes of complicated otitis media. Although study designs varied by primary endpoint measured, age at follow-up, source of middle-ear fluid for culture, case ascertainment, and type of randomization, each clinical trial demonstrated vaccine efficacy against microbiological and/or clinical otitis media. PMID:22701486

Alpha C-telopeptide of type I collagen is associated with subchondral bone turnover and predicts progression of joint space narrowing and osteophytes in osteoarthritis.

PubMed

Huebner, Janet L; Bay-Jensen, Anne C; Huffman, Kim M; He, Yi; Leeming, Diana J; McDaniel, Gary E; Karsdal, Morten A; Kraus, Virginia B

2014-09-01

To evaluate joint tissue remodeling using the urinary collagen biomarkers urinary α-C-telopeptide of type I collagen (α-CTX) and urinary C-telopeptide of type II collagen (CTX-II) and to determine the association of these biomarkers with osteoarthritis (OA) severity, progression, and localized knee bone turnover. Participants (n = 149) with symptomatic and radiographic knee OA underwent fixed-flexion knee radiography at baseline and 3 years, and late-phase bone scintigraphy of both knees at baseline, which were scored semiquantitatively for osteophyte and joint space narrowing (JSN) severity and uptake intensity, with scores summed across knees. Urinary concentrations of α-CTX and CTX-II were determined by enzyme-linked immunosorbent assay. Immunohistochemical analysis of human OA knees was performed to localize the joint tissue origin of the biomarker epitopes. Urinary α-CTX concentrations correlated strongly with the intensity of bone scintigraphic uptake and with JSN progression (risk ratio 13.2) and osteophyte progression (risk ratio 3). Urinary CTX-II concentrations were strongly associated with intensity of bone scintigraphic uptake, with JSN and osteophyte severity, and with OA progression based on osteophyte score. Urinary α-CTX localized primarily to high bone turnover areas in subchondral bone. CTX-II localized to the bone-cartilage interface, the tidemark, and damaged articular cartilage. Baseline urinary α-CTX, which was localized to high turnover areas of subchondral bone, was associated with dynamic bone turnover of knees, as signified by scintigraphy, and progression of both osteophytes and JSN. Urinary CTX-II correlated with JSN and osteophyte severity and progression of osteophytes. To our knowledge, this represents the first report of serologic markers reflecting subchondral bone turnover. These collagen markers may be useful for noninvasive detection and quantification of active subchondral bone turnover and joint remodeling in knee OA. Copyright © 2014 by the American College of Rheumatology.

INVESTIGATION OF BONE MINERALIZATION IN PATIENTS WITH CORONARY HEART DISEASE COMPLICATED BY CHRONIC HEART FAILURE, STAGE II-A.

PubMed

Krynytska, I; Marushchak, M; Zaets, T; Savchenko, I; Habor, H

2017-06-01

The majority of the studies have shown that individuals with cardiovascular diseases have a higher risk of experiencing bone loss and thus greater predisposition to risk of fracture. On the other hand there is growing evidence that individuals with low bone mass have higher mortality for cardiovascular events compared to patients with cardiovascular disease with normal bone mass. This research aims to investigate bone mineralization in patients with coronary heart disease complicated by stage II-A chronic heart failure. The study involved 33 men with coronary heart disease complicated by Stage II-A chronic heart failure. Bone mineral density was measured using dual energy x-ray densitometry of lumbar region of spine. Structural and functional changes of bone tissue of the lumbar spine have been found in 49,2% patients with coronary heart disease complicated by Stage II-A chronic heart failure, in particular, I stage of osteopenia - in 44,6%, II stage of osteopenia - in 27,7%, III stage of osteopenia - in 10,8% and osteoporosis - in 16,9%. It was established the same type of downward trend for BMD decreasing in L1 of patients with different stages of osteopenia, but in case of osteoporosis mineralization decreased equally in all vertebrae.

Inhibition of bone resorption in vitro by antisense RNA and DNA molecules targeted against carbonic anhydrase II or two subunits of vacuolar H(+)-ATPase.

PubMed Central

Laitala, T; Väänänen, H K

1994-01-01

The bone resorbing cells, osteoclasts, express high levels of carbonic anhydrase II (CA II) and vacuolar H(+)-ATPase (V-ATPase) during bone resorption. We have used antisense RNA and DNA molecules targeted against CA II, and against 16- and 60-kD subunits of vacuolar H(+)-ATPase (V-ATPase), to block the expression of these proteins in vitro. Osteoclastic bone resorption was studied in two in vitro culture systems: release of 45Calcium from prelabeled newborn mouse calvaria cultures, and resorption pit assays performed with rat osteoclasts cultured on bovine bone slices. Both antisense RNA and DNA against CA II and the V-ATPase were used to compare their specificities as regards inhibiting bone resorption in vitro. The antisense molecules inhibited the synthesis of these proteins by decreasing the amounts of mRNA in the cells in a highly specific manner. In osteoclast cultures treated with the 16-kD V-ATPase antisense RNA, acidification of an unknown population of intracellular vesicles was highly stimulated. The acidification of these vesicles was not sensitive to amiloride or bafilomycin A1. This suggests the existence of a back-up system for acidification of intracellular vesicles, when the expression of the V-ATPase is blocked. Our results further indicate that blocking the expression of CA II and V-ATPase with antisense RNA or DNA leads to decreased bone resorption. Images PMID:8200964

Inhibitory effect of auranofin (I) and chloroquine (II) on bone degradation induced by the interleukin 1-like (IL-1-like) factor released from rheumatoid synovial tissue (RAST) in vitro

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

Hodges, Y.; Maser, M.R.; Britton, M.C.

1986-03-01

RAST, maintained in organ culture, releases two distinct types of bone resorptive factors and one co-resorptive factor. The first is prostaglandin E/sub 2/ (PGE/sub 2/), while the second is a protein with properties of IL-1. The co-resorptive factor collagenase, cannot induce bone resorption by itself, but augments the bone resorptive activity initiated by either PGE/sub 2/ or the IL-l-like factor. Bone resorptive activity was assessed by measuring the release of /sup 45/Ca from prelabelled rat fetal bones. We investigated the effects of five non-steroidal anti-inflammatory drugs (NSAIDs) and two disease-modifying anti-rheumatic drugs (DMARDs), (I) and (II), on bone degradation mediatedmore » by the IL-l-like factor. None of the NSAIDs tested inhibited bone degradation at 5 x 10/sup -5/ M. On the other hand, both (I) and (II) inhibited bone degradation 60 to 100% at 1 x 10/sup -6/ M and 8 x 10/sup -6/ M respectively. They can inhibit the action of IL-l-like factor on bone at therapeutically attainable concentrations. Additionally, both (I) and (II) block the release of collagenase from the organ culture of RAST with IC/sub 50/s of 5 x 10/sup -6/ M. This unique ability to inhibit collagenase release may contribute to their effectiveness is preventing bone loss in this test model.« less

Dual Regulation of the Small RNA MicC and the Quiescent Porin OmpN in Response to Antibiotic Stress in Escherichia coli

PubMed Central

Dam, Sushovan; Pagès, Jean-Marie

2017-01-01

Antibiotic resistant Gram-negative bacteria are a serious threat for public health. The permeation of antibiotics through their outer membrane is largely dependent on porin, changes in which cause reduced drug uptake and efficacy. Escherichia coli produces two major porins, OmpF and OmpC. MicF and MicC are small non-coding RNAs (sRNAs) that modulate the expression of OmpF and OmpC, respectively. In this work, we investigated factors that lead to increased production of MicC. micC promoter region was fused to lacZ, and the reporter plasmid was transformed into E. coli MC4100 and derivative mutants. The response of micC–lacZ to antimicrobials was measured during growth over a 6 h time period. The data showed that the expression of micC was increased in the presence of β-lactam antibiotics and in an rpoE depleted mutant. Interestingly, the same conditions enhanced the activity of an ompN–lacZ fusion, suggesting a dual transcriptional regulation of micC and the quiescent adjacent ompN. Increased levels of OmpN in the presence of sub-inhibitory concentrations of chemicals could not be confirmed by Western blot analysis, except when analyzed in the absence of the sigma factor σE. We suggest that the MicC sRNA acts together with the σE envelope stress response pathway to control the OmpC/N levels in response to β-lactam antibiotics. PMID:29211019

Application of cranberry concentrate (Vaccinium macrocarpon) to control Escherichia coli O157:H7 in ground beef and its antimicrobial mechanism related to the downregulated slp, hdeA and cfa.

PubMed

Wu, Vivian C H; Qiu, Xujian; de los Reyes, Benildo G; Lin, Chih-Sheng; Pan, Yingjie

2009-02-01

The possible use of cranberry concentrate (CC) as a natural food preservative was studied by examining its antimicrobial effect on the growth of Escherichia coli O157:H7 inoculated in ground beef, its organoleptical effect on beef patties, and its antimicrobial mechanism on the gene regulation level. Inoculated ground beef was added with CC and stored at 4 degrees C for 5 days. Bacteria were detected on day 0, 1, 3, and 5. Cranberry concentrate (2.5%, 5%, and 7.5% w/w) reduced total aerobic bacteria 1.5 log, 2.1 log, and 2.7 log CFU/g and E. coli O157:H7 0.4 log, 0.7 log, and 2.4 log CFU/g, respectively, when compared to the control on day 5. Fifty panelists evaluated the burgers supplemented with CC. No differences in appearance, flavor, and taste were found among burgers with 0%, 2.5%, and 5% CC. The expression of E. coli O157:H7 cyclopropane fatty acyl phospholipid synthase (cfa), hypothetical protein (hdeA), outer membrane porin protein C (ompC), hyperosmotically inducible periplasmic protein (osmY), and outer membrane protein induced after carbon starvation (slp) genes with or without CC (2.5% v/v) treatment was investigated by quantitative real-time PCR. Compared to the control, slp, hdeA, and cfa were markedly downregulated, ompC was slightly downregulated, while osmY was slightly affected.

Cotransplantation of ex vivo expanded progenitors with nonexpanded cord blood cells improves platelet recovery.

PubMed

Émond, Hélène; Boyer, Lucie; Roy, Denis-Claude; Pineault, Nicolas

2012-11-20

Umbilical cord blood (UCB) transplantation is associated with prolonged periods of cytopenia. Ex vivo expansion of hematopoietic stem and progenitor cells (HSPCs) is currently investigated as a mean to accelerate hematological recovery. Contrary to neutrophils, platelet recovery remains problematic. For this reason, we have developed a culture protocol promoting the expansion of megakaryocyte (Mk) progenitors. The objective of this work was to determine whether the expanded (E) UCB HSPCs could accelerate platelet recovery in vivo using a murine HSPC transplantation model. The thrombopoietic activity of UCB and mobilized peripheral blood CD34(+) cells expanded under mild hyperthermia (MH, ie, 39°C) with the optimized megakaryocyte progenitor cocktail (OMPC) diverged significantly from the nonexpanded (NE) cells of origin; E cells provided rapid platelet release, while NE cells strongly contributed to platelet production past 10 days of transplantation. Consequently, the complementary of both cell sources was investigated. Cotransplantation of NE with E UCB cells significantly improved the recovery of human platelets (hPLTs) in vivo due to their complementary and synergistic thrombopoietic activities. Moreover, short-term human bone marrow (BM) reconstitution was also improved. Finally, we show that early hPLT release is dependent on Mk-primed cells and that E cells do not act as accessory cells, but have a more active role. In conclusion, hPLT recovery and short-term BM engraftment can be efficiently improved by the cotransplantation of Mk-primed UCB cells with NE HSPCs in a murine transplantation model.

Fracture characterization of human cortical bone under mode II loading using the end-notched flexure test.

PubMed

Silva, F G A; de Moura, M F S F; Dourado, N; Xavier, J; Pereira, F A M; Morais, J J L; Dias, M I R; Lourenço, P J; Judas, F M

2017-08-01

Fracture characterization of human cortical bone under mode II loading was analyzed using a miniaturized version of the end-notched flexure test. A data reduction scheme based on crack equivalent concept was employed to overcome uncertainties on crack length monitoring during the test. The crack tip shear displacement was experimentally measured using digital image correlation technique to determine the cohesive law that mimics bone fracture behavior under mode II loading. The developed procedure was validated by finite element analysis using cohesive zone modeling considering a trapezoidal with bilinear softening relationship. Experimental load-displacement curves, resistance curves and crack tip shear displacement versus applied displacement were used to validate the numerical procedure. The excellent agreement observed between the numerical and experimental results reveals the appropriateness of the proposed test and procedure to characterize human cortical bone fracture under mode II loading. The proposed methodology can be viewed as a novel valuable tool to be used in parametric and methodical clinical studies regarding features (e.g., age, diseases, drugs) influencing bone shear fracture under mode II loading.

Renin inhibitor aliskiren exerts beneficial effect on trabecular bone by regulating skeletal renin-angiotensin system and kallikrein-kinin system in ovariectomized mice.

PubMed

Zhang, Y; Wang, L; Song, Y; Zhao, X; Wong, M S; Zhang, W

2016-03-01

The skeletal renin-angiotensin system contributes to the development of osteoporosis. The renin inhibitor aliskiren exhibited beneficial effects on trabecular bone of osteoporotic mice, and this action might be mediated through angiotensin and bradykinin receptor pathways. This study implies the potential application of renin inhibitor in the management for postmenopausal osteoporosis. The skeletal renin-angiotensin system plays key role in the pathological process of osteoporosis. The present study is designed to elucidate the effect of renin inhibitor aliskiren on trabecular bone and its potential action mechanism in ovariectomized (OVX) mice. The OVX mice were treated with low dose (5 mg/kg) or high dose (25 mg/kg) of aliskiren or its vehicle for 8 weeks. The bone turnover markers were measured by ELISA. The structural parameters of trabecular bone at lumbar vertebra (LV) and distal femoral metaphysis were measured by micro-CT. The expression of messenger RNA (mRNA) and protein was studied by RT-PCR and immunoblotting, respectively. Aliskiren treatment reduced urinary excretion of calcium and serum level of tartrate-resistant acid phosphatase in OVX mice. The treatment with aliskiren significantly increased bone volume (BV/TV) and connectivity density (Conn.D) of trabecular bone at LV-2 and LV-5 as well as dramatically enhanced BV/TV, Conn.D, bone mineral density (BMD/BV) and decreased bone surface (BS/BV) at the distal femoral end. Aliskiren significantly down-regulated the expression of angiotensinogen, angiotensin II (Ang II), Ang II type 1 receptor, bradykinin receptor (BR)-1, and osteocytic-specific gene sclerostin as well as the osteoclast-specific genes, including carbonic anhydrase II, matrix metalloproteinase-9, and cathepsin K. This study revealed that renin inhibitor aliskiren exhibited the beneficial effects on trabecular bone of ovariectomy-induced osteoporotic mice, and the underlying mechanism for this action might be mediated through Ang II and BR signaling pathways in bone.

Fcγ receptor-mediated influx of S100A8/A9-producing neutrophils as inducer of bone erosion during antigen-induced arthritis.

PubMed

Di Ceglie, Irene; Ascone, Giuliana; Cremers, Niels A J; Sloetjes, Annet W; Walgreen, Birgitte; Vogl, Thomas; Roth, Johannes; Verbeek, J Sjef; van de Loo, Fons A J; Koenders, Marije I; van der Kraan, Peter M; Blom, Arjen B; van den Bosch, Martijn H J; van Lent, Peter L E M

2018-05-02

Osteoclast-mediated bone erosion is a central feature of rheumatoid arthritis (RA). Immune complexes, present in a large percentage of patients, bind to Fcγ receptors (FcγRs), thereby modulating the activity of immune cells. In this study, we investigated the contribution of FcγRs, and FcγRIV in particular, during antigen-induced arthritis (AIA). AIA was induced in knee joints of wild-type (WT), FcγRI,II,III -/- , and FcγRI,II,III,IV -/- mice. Bone destruction, numbers of tartrate-resistant acid phosphatase-positive (TRAP + ) osteoclasts, and inflammation were evaluated using histology; expression of the macrophage marker F4/80, neutrophil marker NIMPR14, and alarmin S100A8 was evaluated using immunohistochemistry. The percentage of osteoclast precursors in the bone marrow was determined using flow cytometry. In vitro osteoclastogenesis was evaluated with TRAP staining, and gene expression was assessed using real-time PCR. FcγRI,II,III,IV -/- mice showed decreased bone erosion compared with WT mice during AIA, whereas both the humoral and cellular immune responses against methylated bovine serum albumin were not impaired in FcγRI,II,III,IV -/- mice. The percentage of osteoclast precursors in the bone marrow of arthritic mice and their ability to differentiate into osteoclasts in vitro were comparable between FcγRI,II,III,IV -/- and WT mice. In line with these observations, numbers of TRAP + osteoclasts on the bone surface during AIA were comparable between the two groups. Inflammation, a process that strongly activates osteoclast activity, was reduced in FcγRI,II,III,IV -/- mice, and of note, mainly decreased numbers of neutrophils were present in the joint. In contrast to FcγRI,II,III,IV -/- mice, AIA induction in knee joints of FcγRI,II,III -/- mice resulted in increased bone erosion, inflammation, and numbers of neutrophils, suggesting a crucial role for FcγRIV in the joint pathology by the recruitment of neutrophils. Finally, significant correlations were found between bone erosion and the number of neutrophils present in the joint as well as between bone erosion and the number of S100A8-positive cells, with S100A8 being an alarmin strongly produced by neutrophils that stimulates osteoclast resorbing activity. FcγRs play a crucial role in the development of bone erosion during AIA by inducing inflammation. In particular, FcγRIV mediates bone erosion in AIA by inducing the influx of S100A8/A9-producing neutrophils into the arthritic joint.

CXCR6 plays a critical role in angiotensin II-induced renal injury and fibrosis.

PubMed

Xia, Yunfeng; Jin, Xiaogao; Yan, Jingyin; Entman, Mark L; Wang, Yanlin

2014-07-01

Recent studies have shown that angiotensin II (Ang II) plays a critical role in the pathogenesis and progression of hypertensive kidney disease. However, the signaling mechanisms are poorly understood. In this study, we investigated the role of CXCR6 in Ang II-induced renal injury and fibrosis. Wild-type and CXCR6-green fluorescent protein (GFP) knockin mice were treated with Ang II via subcutaneous osmotic minipumps at 1500 ng/kg per minute after unilateral nephrectomy for ≤ 4 weeks. Wild-type and CXCR6-GFP knockin mice had virtually identical blood pressure at baseline. Ang II treatment led to an increase in blood pressure that was similar between wild-type and CXCR6-GFP knockin mice. CXCR6-GFP knockin mice were protected from Ang II-induced renal dysfunction, proteinuria, and fibrosis. CXCR6-GFP knockin mice accumulated fewer bone marrow-derived fibroblasts and myofibroblasts and produced less extracellular matrix protein in the kidneys after Ang II treatment. Furthermore, CXCR6-GFP knockin mice exhibited fewer F4/80(+) macrophages and CD3(+) T cells and expressed less proinflammatory cytokines in the kidneys after Ang II treatment. Finally, wild-type mice engrafted with CXCR6(-/-) bone marrow cells displayed fewer bone marrow-derived fibroblasts, macrophages, and T cells in the kidney after Ang II treatment when compared with wild-type mice engrafted with CXCR6(+/+) bone marrow cells. Our results indicate that CXCR6 plays a pivotal role in the development of Ang II-induced renal injury and fibrosis through regulation of macrophage and T-cell infiltration and bone marrow-derived fibroblast accumulation. © 2014 American Heart Association, Inc.

CXCR6 Plays a Critical Role in Angiotensin II-induced Renal Injury and Fibrosis

PubMed Central

Xia, Yunfeng; Jin, Xiaogao; Yan, Jingyin; Entman, Mark L.; Wang, Yanlin

2014-01-01

Objective Recent studies have shown that angiotensin II (Ang II) plays a critical role in the pathogenesis and progression of hypertensive kidney disease. However, the signaling mechanisms are poorly understood. In this study, we investigated the role of CXCR6 in Ang II-induced renal injury and fibrosis. Approach and Results Wild-type and CXCR6-GFP knockin mice were treated with Ang II via subcutaneous osmotic minipumps at 1500 ng/kg/min after unilateral nephrectomy for up to 4 weeks. WT and CXCR6-GFP knockin mice had virtually identical blood pressure at baseline. Ang II treatment led to an increase in blood pressure that was similar between WT and CXCR6-GFP knockin mice. CXCR6-GFP knockin mice were protected from Ang II-induced renal dysfunction, proteinuria, and fibrosis. CXCR6-GFP knockin mice accumulated fewer bone marrow-derived fibroblasts and myofibroblasts and produced less extracellular matrix protein in the kidneys following Ang II treatment. Furthermore, CXCR6-GFP knockin mice exhibited fewer F4/80+ macrophages and CD3+ T cells and expressed less proinflammatory cytokines in the kidneys after Ang II treatment. Finally, wild-type mice engrafted with CXCR6−/− bone marrow cells displayed fewer bone marrow-derived fibroblasts, macrophages, and T cells in the kidney after Ang II treatment compared with wild-type mice engrafted with CXCR6+/+ bone marrow cells. Conclusions Our results indicate that CXCR6 plays a pivotal role in the development of Ang II-induced renal injury and fibrosis through regulation of macrophage and T cell infiltration and bone marrow-derived fibroblast accumulation. PMID:24855055

Alveolar bone thickness and lower incisor position in skeletal Class I and Class II malocclusions assessed with cone-beam computed tomography

PubMed Central

Ucar, Faruk Izzet; Buyuk, Suleyman Kutalmis; Ozer, Torun; Uysal, Tancan

2013-01-01

Objective To evaluate lower incisor position and bony support between patients with Class II average- and high-angle malocclusions and compare with the patients presenting Class I malocclusions. Methods CBCT records of 79 patients were divided into 2 groups according to sagittal jaw relationships: Class I and II. Each group was further divided into average- and high-angle subgroups. Six angular and 6 linear measurements were performed. Independent samples t-test, Kruskal-Wallis, and Dunn post-hoc tests were performed for statistical comparisons. Results Labial alveolar bone thickness was significantly higher in Class I group compared to Class II group (p = 0.003). Lingual alveolar bone angle (p = 0.004), lower incisor protrusion (p = 0.007) and proclination (p = 0.046) were greatest in Class II average-angle patients. Spongious bone was thinner (p = 0.016) and root apex was closer to the labial cortex in high-angle subgroups when compared to the Class II average-angle subgroup (p = 0.004). Conclusions Mandibular anterior bony support and lower incisor position were different between average- and high-angle Class II patients. Clinicians should be aware that the range of lower incisor movement in high-angle Class II patients is limited compared to average- angle Class II patients. PMID:23814708

Alveolar bone thickness and lower incisor position in skeletal Class I and Class II malocclusions assessed with cone-beam computed tomography.

PubMed

Baysal, Asli; Ucar, Faruk Izzet; Buyuk, Suleyman Kutalmis; Ozer, Torun; Uysal, Tancan

2013-06-01

To evaluate lower incisor position and bony support between patients with Class II average- and high-angle malocclusions and compare with the patients presenting Class I malocclusions. CBCT records of 79 patients were divided into 2 groups according to sagittal jaw relationships: Class I and II. Each group was further divided into average- and high-angle subgroups. Six angular and 6 linear measurements were performed. Independent samples t-test, Kruskal-Wallis, and Dunn post-hoc tests were performed for statistical comparisons. Labial alveolar bone thickness was significantly higher in Class I group compared to Class II group (p = 0.003). Lingual alveolar bone angle (p = 0.004), lower incisor protrusion (p = 0.007) and proclination (p = 0.046) were greatest in Class II average-angle patients. Spongious bone was thinner (p = 0.016) and root apex was closer to the labial cortex in high-angle subgroups when compared to the Class II average-angle subgroup (p = 0.004). Mandibular anterior bony support and lower incisor position were different between average- and high-angle Class II patients. Clinicians should be aware that the range of lower incisor movement in high-angle Class II patients is limited compared to average- angle Class II patients.

[Polarized microscopic observation of the collagen change in bone healing during bone lengthening].

PubMed

Zou, Pei; Li, Junhui; Li, Zhuyi

2006-01-01

To investigate the feature and regularity of the collagen change in bone healing during bone lengthening. Bone lengthening model was made in the middle segment of the rabbit tibia. Five days after the model was established, the bone was lengthened 1.5 mm per day for 14 days. The rabbits were put to death after elongation, 7, 14, 21, 30, 40, 50, 60 and 70 days after elongation. The distracted area of the bone was imbedded with paraffin. After being stained by the picric acid-sirius red staining, the slice was observed under polarized microscope. The features of the collagen change in the distracted bone were as follows: (1) In the fibrous tissue of the distracted area during lengthening period and the early stage after lengthening, there was not only collagen III but also much collagen I. (2) Collagen I , II and III were observed in the cartilage. (3) Collagen I, II and III were also observed in the pseudo-growth plate. (4) Collagen I took the dominance during lengthening period and the late stage after lengthening. New bone formation in bone lengthening is under the distracted force, so the collagen changes have different features compared with that in fracture healing. Collagen I, II and III can be identified by picric acid-sirius red staining and polarized microscope, so a new method for studying the collagen typing in bone repairing is provided.

Construction and phase I clinical evaluation of the safety and immunogenicity of a candidate enterotoxigenic Escherichia coli vaccine strain expressing colonization factor antigen CFA/I.

PubMed

Turner, Arthur K; Beavis, Juliet C; Stephens, Jonathan C; Greenwood, Judith; Gewert, Cornelia; Thomas, Nicola; Deary, Alison; Casula, Gabriella; Daley, Alexandra; Kelly, Paul; Randall, Roger; Darsley, Michael J

2006-02-01

Oral delivery of toxin-negative derivatives of enterotoxigenic Escherichia coli (ETEC) that express colonization factor antigens (CFA) with deletions of the aroC, ompC, ompF, and toxin genes may be an effective approach to vaccination against ETEC-associated diarrhea. We describe the creation and characterization of an attenuated CFA/I-expressing ETEC vaccine candidate, ACAM2010, from a virulent isolate in which the heat-stable enterotoxin (ST) and CFA/I genes were closely linked and on the same virulence plasmid as the enteroaggregative E. coli heat-stable toxin (EAST1) gene. A new suicide vector (pJCB12) was constructed and used to delete the ST and EAST1 genes and to introduce defined deletion mutations into the aroC, ompC, and ompF chromosomal genes. A phase I trial, consisting of an open-label dose escalation phase in 18 adult outpatient volunteers followed by a placebo-controlled double-blind phase in an additional 31 volunteers, was conducted. The vaccine was administered in two formulations, fresh culture and frozen suspension. These were both well tolerated, with no evidence of significant adverse events related to vaccination. Immunoglobulin A (IgA) and IgG antibody-secreting cells specific for CFA/I were assayed by ELISPOT. Positive responses (greater than twofold increase) were seen in 27 of 37 (73%) subjects who received the highest dose level of vaccine (nominally 5 x 10(9) CFU). Twenty-nine of these volunteers were secreting culturable vaccine organisms at day 3 following vaccination; five were still positive on day 7, with a single isolation on day 13. This live attenuated bacterial vaccine is safe and immunogenic in healthy adult volunteers.

Telomerase deficiency in bone marrow-derived cells attenuates angiotensin II-induced abdominal aortic aneurysm formation.

PubMed

Findeisen, Hannes M; Gizard, Florence; Zhao, Yue; Cohn, Dianne; Heywood, Elizabeth B; Jones, Karrie L; Lovett, David H; Howatt, Deborah A; Daugherty, Alan; Bruemmer, Dennis

2011-02-01

Abdominal aortic aneurysms (AAA) are an age-related vascular disease and an important cause of morbidity and mortality. In this study, we sought to determine whether the catalytic component of telomerase, telomerase reverse transcriptase (TERT), modulates angiotensin (Ang) II-induced AAA formation. Low-density lipoprotein receptor-deficient (LDLr-/-) mice were lethally irradiated and reconstituted with bone marrow-derived cells from TERT-deficient (TERT-/-) mice or littermate wild-type mice. Mice were placed on a diet enriched in cholesterol, and AAA formation was quantified after 4 weeks of Ang II infusion. Repopulation of LDLr-/- mice with TERT-/- bone marrow-derived cells attenuated Ang II-induced AAA formation. TERT-deficient recipient mice revealed modest telomere attrition in circulating leukocytes at the study end point without any overt effect of the donor genotype on white blood cell counts. In mice repopulated with TERT-/- bone marrow, aortic matrix metalloproteinase-2 (MMP-2) activity was reduced, and TERT-/- macrophages exhibited decreased expression and activity of MMP-2 in response to stimulation with Ang II. Finally, we demonstrated in transient transfection studies that TERT overexpression activates the MMP-2 promoter in macrophages. TERT deficiency in bone marrow-derived macrophages attenuates Ang II-induced AAA formation in LDLr-/- mice and decreases MMP-2 expression. These results point to a previously unrecognized role of TERT in the pathogenesis of AAA.

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

Ecarot-Charrier, B.; Bouchard, F.; Delloye, C.

Isolated mouse osteoblasts that retain their osteogenic activity in culture were incubated with (35S) sulfate. Two radiolabeled proteins, in addition to proteoglycans, were extracted from the calcified matrix of osteoblast cultures. All the sulfate label in both proteins was in the form of tyrosine sulfate as assessed by amino acid analysis and thin layer chromatography following alkaline hydrolysis. The elution behavior on DEAE-Sephacel of the major sulfated protein and the apparent Mr on sodium dodecyl sulfate gels were characteristic of bone sialoprotein II extracted from rat. This protein was shown to cross-react with an antiserum raised against bovine bone sialoproteinmore » II, indicating that bone sialoprotein II synthesized by cultured mouse osteoblasts is a tyrosine-sulfated protein. The minor sulfated protein was tentatively identified as bone sialoprotein I or osteopontin based on its elution properties on DEAE-Sephacel and anomalous behavior on sodium dodecyl sulfate gels similar to those reported for rat bone sialoprotein I.« less

21 CFR 888.3027 - Polymethylmethacrylate (PMMA) bone cement.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Polymethylmethacrylate (PMMA) bone cement. 888... Polymethylmethacrylate (PMMA) bone cement. (a) Identification. Polymethylmethacrylate (PMMA) bone cement is a device... metallic prosthetic implants to living bone. (b) Classification. Class II (special controls). The special...

21 CFR 888.3027 - Polymethylmethacrylate (PMMA) bone cement.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Polymethylmethacrylate (PMMA) bone cement. 888... Polymethylmethacrylate (PMMA) bone cement. (a) Identification. Polymethylmethacrylate (PMMA) bone cement is a device... metallic prosthetic implants to living bone. (b) Classification. Class II (special controls). The special...

21 CFR 888.3027 - Polymethylmethacrylate (PMMA) bone cement.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Polymethylmethacrylate (PMMA) bone cement. 888... Polymethylmethacrylate (PMMA) bone cement. (a) Identification. Polymethylmethacrylate (PMMA) bone cement is a device... metallic prosthetic implants to living bone. (b) Classification. Class II (special controls). The special...

21 CFR 888.3027 - Polymethylmethacrylate (PMMA) bone cement.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Polymethylmethacrylate (PMMA) bone cement. 888... Polymethylmethacrylate (PMMA) bone cement. (a) Identification. Polymethylmethacrylate (PMMA) bone cement is a device... metallic prosthetic implants to living bone. (b) Classification. Class II (special controls). The special...

21 CFR 888.3027 - Polymethylmethacrylate (PMMA) bone cement.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Polymethylmethacrylate (PMMA) bone cement. 888... Polymethylmethacrylate (PMMA) bone cement. (a) Identification. Polymethylmethacrylate (PMMA) bone cement is a device... metallic prosthetic implants to living bone. (b) Classification. Class II (special controls). The special...

Sclerostin antibody inhibits skeletal deterioration in mice exposed to partial weight-bearing

NASA Astrophysics Data System (ADS)

Spatz, J. M.; Ellman, R.; Cloutier, A. M.; Louis, L.; van Vliet, M.; Dwyer, D.; Stolina, M.; Ke, H. Z.; Bouxsein, M. L.

2017-02-01

Whereas much is known regarding the musculoskeletal responses to full unloading, little is known about the physiological effects and response to pharmacological agents in partial unloading (e.g. Moon and Mars) environments. To address this, we used a previously developed ground-based model of partial weight-bearing (PWB) that allows chronic exposure to reduced weight-bearing in mice to determine the effects of murine sclerostin antibody (SclAbII) on bone microstructure and strength across different levels of mechanical unloading. We hypothesize that treatment with SclAbII would improve bone mass, microarchitecture and strength in all loading conditions, but that there would be a greater skeletal response in the normally loaded mice than in partially unloaded mice suggesting the importance of combined countermeasures for exploration-class long duration spaceflight missions. Eleven-week-old female mice were assigned to one of four loading groups: normal weight-bearing controls (CON) or weight-bearing at 20% (PWB20), 40% (PWB40) or 70% (PWB70) of normal. Mice in each group received either SclAbII (25 mg/kg) or vehicle (VEH) via twice weekly subcutaneous injection for 3 weeks. In partially-unloaded VEH-treated groups, leg BMD decreased -5 to -10% in a load-dependent manner. SclAbII treatment completely inhibited bone deterioration due to PWB, with bone properties in SclAbII-treated groups being equal to or greater than those of CON, VEH-treated mice. SclAbII treatment increased leg BMD from +14 to +18% in the PWB groups and 30 ± 3% in CON (p < 0.0001 for all). Trabecular bone volume, assessed by μCT at the distal femur, was lower in all partially unloaded VEH-treated groups vs. CON-VEH (p < 0.05), and was 2-3 fold higher in SclAbII-treated groups (p < 0.001). Midshaft femoral strength was also significantly higher in SclAbII vs. VEH-groups in all-loading conditions. These results suggest that greater weight bearing leads to greater benefits of SclAbII on bone mass, particularly in the trabecular compartment. Altogether, these results demonstrate the efficacy of sclerostin antibody therapy in preventing astronaut bone loss during terrestrial solar system exploration.

Sclerostin antibody inhibits skeletal deterioration in mice exposed to partial weight-bearing.

PubMed

Spatz, J M; Ellman, R; Cloutier, A M; Louis, L; van Vliet, M; Dwyer, D; Stolina, M; Ke, H Z; Bouxsein, M L

2017-02-01

Whereas much is known regarding the musculoskeletal responses to full unloading, little is known about the physiological effects and response to pharmacological agents in partial unloading (e.g. Moon and Mars) environments. To address this, we used a previously developed ground-based model of partial weight-bearing (PWB) that allows chronic exposure to reduced weight-bearing in mice to determine the effects of murine sclerostin antibody (SclAbII) on bone microstructure and strength across different levels of mechanical unloading. We hypothesize that treatment with SclAbII would improve bone mass, microarchitecture and strength in all loading conditions, but that there would be a greater skeletal response in the normally loaded mice than in partially unloaded mice suggesting the importance of combined countermeasures for exploration-class long duration spaceflight missions. Eleven-week-old female mice were assigned to one of four loading groups: normal weight-bearing controls (CON) or weight-bearing at 20% (PWB20), 40% (PWB40) or 70% (PWB70) of normal. Mice in each group received either SclAbII (25mg/kg) or vehicle (VEH) via twice weekly subcutaneous injection for 3 weeks. In partially-unloaded VEH-treated groups, leg BMD decreased -5 to -10% in a load-dependent manner. SclAbII treatment completely inhibited bone deterioration due to PWB, with bone properties in SclAbII-treated groups being equal to or greater than those of CON, VEH-treated mice. SclAbII treatment increased leg BMD from +14 to +18% in the PWB groups and 30 ± 3% in CON (p< 0.0001 for all). Trabecular bone volume, assessed by μCT at the distal femur, was lower in all partially unloaded VEH-treated groups vs. CON-VEH (p< 0.05), and was 2-3 fold higher in SclAbII-treated groups (p< 0.001). Midshaft femoral strength was also significantly higher in SclAbII vs. VEH-groups in all-loading conditions. These results suggest that greater weight bearing leads to greater benefits of SclAbII on bone mass, particularly in the trabecular compartment. Altogether, these results demonstrate the efficacy of sclerostin antibody therapy in preventing astronaut bone loss during terrestrial solar system exploration. Copyright © 2017 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

Elastomeric enriched biodegradable polyurethane sponges for critical bone defects: a successful case study reducing donor site morbidity.

PubMed

Lavrador, Catarina; Mascarenhas, Ramiro; Coelho, Paulo; Brites, Cláudia; Pereira, Alfredo; Gogolewski, Sylwester

2016-03-01

Bone substitutes have been a critical issue as the natural source can seldom provide enough bone to support full healing. No bone substitute complies with all necessary functions and characteristics that an autograft does. Polyurethane sponges have been used as a surgical alternative to cancellous bone grafts for critical bone defect donor sites. Critical bone defects were created on the tibial tuberosity and iliac crest using an ovine model. In group I (control-untreated), no bone regeneration was observed in any animal. In group II (defects left empty but covered with a microporous polymeric membrane), the new bone bridged the top ends in all animals. In groups III and IV, bone defects were implanted with polyurethane scaffolds modified with biologically active compounds, and bone regeneration was more efficient than in group II. In groups III and IV there were higher values of bone regeneration specific parameters used for evaluation (P < 0.05) although the comparison between these groups was not possible. The results obtained in this study suggest that biodegradable polyurethane substitutes modified with biologically active substances may offer an alternative to bone graft, reducing donor site morbidity associated with autogenous cancellous bone harvesting.

[Morphological analysis of alveolar bone of anterior mandible in high-angle skeletal class II and class III malocclusions assessed with cone-beam computed tomography].

PubMed

Ma, J; Jiang, J H

2018-02-18

To evaluate the difference of features of alveolar bone support under lower anterior teeth between high-angle adults with skeletal class II malocclusions and high-angle adults presenting skeletal class III malocclusions by using cone-beam computed tomography (CBCT). Patients who had taken the images of CBCT were selected from the Peking University School and Hospital of Stomatology between October 2015 and August 2017. The CBCT archives from 62 high-angle adult cases without orthodontic treatment were divided into two groups based on their sagittal jaw relationships: skeletal class II and skeletal class III. vertical bone level (VBL), alveolar bone area (ABA), and the width of alveolar bone were measured respectively at the 2 mm, 4 mm, 6 mm below the cemento-enamel junction (CEJ) level and at the apical level. After that, independent samples t-tests were conducted for statistical comparisons. The ABA of the mandibular alveolar bone in the area of lower anterior teeth was significantly thinner in the patients of skeletal class III than those of skeletal class II, especially in terms of the apical ABA, total ABA on the labial and lingual sides and the ABA at 6 mm below CEJ level on the lingual side (P<0.05). The thickness of the alveolar bone of mandibular anterior teeth was significantly thinner in the subjects of skeletal class III than those of skeletal class II, especially regarding the apical level on the labial and lingual side and at the level of 4 mm, 6 mm below CEJ level on the lingual side (P<0.05). The ABA and the thickness of the alveolar bone of mandibular anterior teeth were significantly thinner in the group of skeletal class III adult patients with high-angle when compared with the sample of high-angle skeletal class II adult cases. We recommend orthodontists to be more cautious in treatment of high-angle skeletal class III patients, especially pay attention to control the torque of lower anterior teeth during forward and backward movement, in case that the apical root might be absorbed or fenestration happen in the area of lower anterior teeth.

Effects of beta-lactamases and omp mutation on susceptibility to beta-lactam antibiotics in Escherichia coli.

PubMed Central

Hiraoka, M; Okamoto, R; Inoue, M; Mitsuhashi, S

1989-01-01

Four types of beta-lactamases consisting of a penicillinase type I (TEM-1), a penicillinase type II (OXA-1), a cephalosporinase of Citrobacter freundii, and a cephalosporinase of Proteus vulgaris were introduced into Escherichia coli MC4100 and its omp mutants, MH1160 (MC4100 ompR1) and MH760 (MC4100 ompR2), by transformation. Effects of the combination of the omp mutations and these beta-lactamases on the susceptibility of E. coli strains were studied with 15 beta-lactam antibiotics including cephalosporins, cephamycins, penicillins, imipenem, and aztreonam. The ompR1 mutant, MH1160, lacks OmpF and OmpC, and it showed reduced susceptibility to 11 of the 15 beta-lactam agents. The reduction in susceptibility to cefoxitin, moxalactam, and flomoxef was much greater than reduction in susceptibility to the other agents. When the ompR1 mutant produced the cephalosporinase of C. freundii, the susceptibility of the mutant to 12 of the 15 beta-lactam antibiotics decreased. The reduction in susceptibility of MH1160 to 10 of the 12 agents affected by the enzyme was two- to fourfold greater than that observed in MC4100. Such a synergistic effect was also observed with the cephalosporinase of P. vulgaris and ompR1 mutation against six cephalosporins, moxalactam, and aztreonam. Images PMID:2658786

Class I and class II major histocompatibility molecules play a role in bone marrow-derived macrophage development

NASA Technical Reports Server (NTRS)

Armstrong, J. W.; Simske, S. J.; Beharka, A. A.; Balch, S.; Luttges, M. W.; Chapes, S. K.; Spooner, B. S. (Principal Investigator)

1994-01-01

Class I and class II major histocompatibility complex (MHC) molecules play significant roles in T cell development and immune function. We show that MHCI- and MHCII-deficient mice have low numbers of macrophage precursors and circulating monocytes, as well as abnormal bone marrow cell colony-stimulating factor type 1 secretion and bone composition. We suggest that MHCI and MHCII molecules play a significant role in macrophage development.

Bone x-ray

MedlinePlus

... different views of the bone may be uncomfortable. Why the Test is Performed A bone x-ray ... neoplasia (MEN) II Multiple myeloma Osgood-Schlatter disease Osteogenesis imperfecta Osteomalacia Paget's disease Primary hyperparathyroidism Rickets Risks There ...

21 CFR 888.3045 - Resorbable calcium salt bone void filler device.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Resorbable calcium salt bone void filler device... salt bone void filler device. (a) Identification. A resorbable calcium salt bone void filler device is... entitled “Class II Special Controls Guidance: Resorbable Calcium Salt Bone Void Filler Device; Guidance for...

21 CFR 888.3045 - Resorbable calcium salt bone void filler device.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Resorbable calcium salt bone void filler device... salt bone void filler device. (a) Identification. A resorbable calcium salt bone void filler device is... entitled “Class II Special Controls Guidance: Resorbable Calcium Salt Bone Void Filler Device; Guidance for...

21 CFR 888.3045 - Resorbable calcium salt bone void filler device.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Resorbable calcium salt bone void filler device... salt bone void filler device. (a) Identification. A resorbable calcium salt bone void filler device is... entitled “Class II Special Controls Guidance: Resorbable Calcium Salt Bone Void Filler Device; Guidance for...

21 CFR 888.3045 - Resorbable calcium salt bone void filler device.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Resorbable calcium salt bone void filler device... salt bone void filler device. (a) Identification. A resorbable calcium salt bone void filler device is... entitled “Class II Special Controls Guidance: Resorbable Calcium Salt Bone Void Filler Device; Guidance for...

21 CFR 888.3045 - Resorbable calcium salt bone void filler device.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Resorbable calcium salt bone void filler device... salt bone void filler device. (a) Identification. A resorbable calcium salt bone void filler device is... entitled “Class II Special Controls Guidance: Resorbable Calcium Salt Bone Void Filler Device; Guidance for...

Nuclear chromatin-concentrated osteoblasts in renal bone diseases.

PubMed

Kazama, Junichiro James; Yamamoto, Suguru; Narita, Ichiei; Kurihara, Satoshi

2011-06-01

The morphological appearance of an osteoblast largely alters with its differentiation and maturation, along with the change of cell function. We quantitatively observed the osteoblast morphology and compared it with bone metabolism. Biopsied iliac bone samples obtained from 77 dialysis patients (14 mild change, 37 osteitis fibrosa, 2 osteomalacia, 8 mixed, and 16 adynamic bone) were included in the study. Osteoblast appearances were classified into three groups: (i) type II and III osteoblasts, namely, active osteoblasts characterized by cuboidal or columnar shapes with or without a nuclear clear zone; (ii) type IV osteoblasts, lining osteoblasts characterized by extremely thin cytoplasm; and (iii) type V osteoblasts, apoptotic osteoblasts characterized by nuclear chromatin concentration. The results were quantitatively expressed as the length of bone surface covered by each type of osteoblasts. The type II and III osteoblasts were predominant in osteitis fibrosa, mixed, and mild change. The type IV osteoblasts were overwhelmingly predominant in adynamic bone. The type V osteoblasts appeared most frequently in osteitis fibrosa, followed by mixed and mild change. Both absolute and relative lengths of bone surface covered by the type V osteoblasts were significantly higher in the high-turnover bone group (osteitis fibrosa and mixed) than the low-turnover bone group (adynamic bone and osteomalacia). The type V osteoblasts were slightly correlated with serum intact parathyroid hormone levels. In conclusion, a high bone-turnover condition seems to be associated with the promotion of osteoblastic apoptosis in dialysis patients. This finding may explain the fact that osteopenia develops faster in CKD patients with high turnover of bone. © 2011 The Authors. Therapeutic Apheresis and Dialysis © 2011 International Society for Apheresis.

Permanence of diced cartilage, bone dust and diced cartilage/bone dust mixture in experimental design in twelve weeks.

PubMed

Islamoglu, Kemal; Dikici, Mustafa Bahadir; Ozgentas, Halil Ege

2006-09-01

Bone dust and diced cartilage are used for contour restoration because their minimal donor site morbidity. The purpose of this study is to investigate permanence of bone dust, diced cartilage and bone dust/diced cartilage mixture in rabbits over 12 weeks. New Zealand white rabbits were used for this study. There were three groups in the study: Group I: 1 mL bone dust. Group II: 1 mL diced cartilage. Group III: 0.5 mL bone dust + 0.5 mL diced cartilage mixture. They were placed into subcutaneous tissue of rabbits and removed 12 weeks later. The mean volumes of groups were 0.23 +/- 0.08 mL in group I, 0.60 +/- 0.12 mL in group II and 0.36 +/- 0.10 mL in group III. The differences between groups were found statistically significant. In conclusion, diced cartilage was found more reliable than bone dust aspect of preserving its volume for a long period in this study.

Insulin-like growth factor-II regulates bone sialoprotein gene transcription.

PubMed

Choe, Jin; Sasaki, Yoko; Zhou, Liming; Takai, Hideki; Nakayama, Yohei; Ogata, Yorimasa

2016-09-01

Insulin-like growth factor-I and -II (IGF-I and IGF-II) have been found in bone extracts of several different species, and IGF-II is the most abundant growth factor stored in bone. Bone sialoprotein (BSP) is a noncollagenous extracellular matrix glycoprotein associated with mineralized connective tissues. In this study, we have investigated the regulation of BSP transcription by IGF-II in rat osteoblast-like ROS17/2.8 cells. IGF-II (50 ng/ml) increased BSP mRNA and protein levels after 6-h stimulation, and enhanced luciferase activities of the constructs pLUC3 (-116 to +60), pLUC4 (-425 to +60), pLUC5 (-801 to +60) and pLUC6 (-938 to +60). Effects of IGF-II were inhibited by tyrosine kinase, extracellular signal-regulated kinase1/2 and phosphatidylinositol 3-kinase inhibitors, and abrogated by 2-bp mutations in cAMP response element (CRE), FGF2 response element (FRE) and homeodomain protein-binding site (HOX). The results of gel shift assays showed that nuclear proteins binding to CRE, FRE and HOX sites were increased by IGF-II (50 ng/ml) at 3 and 6 h. CREB1, phospho-CREB1, c-Fos and c-Jun antibodies disrupted the formation of the CRE-protein complexes. Dlx5 and Runx2 antibodies disrupted the FRE- and HOX-protein complex formations. These studies therefore demonstrated that IGF-II increased BSP transcription by targeting CRE, FRE and HOX elements in the proximal promoter of the rat BSP gene. Moreover, phospho-CREB1, c-Fos, c-Jun, Dlx5 and Runx2 transcription factors appear to be key regulators of IGF-II effects on BSP transcription.

Autologous Bone Marrow Concentrates and Concentrated Growth Factors Accelerate Bone Regeneration After Enucleation of Mandibular Pathologic Lesions.

PubMed

Talaat, Wael M; Ghoneim, Mohamed M; Salah, Omar; Adly, Osama A

2018-02-23

Stem cell therapy is a revolutionary new way to stimulate mesenchymal tissue regeneration. The platelets concentrate products started with platelet-rich plasma (PRP), followed by platelet-rich fibrin (PRF), whereas concentrated growth factors (CGF) are the latest generation of the platelets concentrate products which were found in 2011. The aim of the present study was to evaluate the potential of combining autologous bone marrow concentrates and CGF for treatment of bone defects resulting from enucleation of mandibular pathologic lesions. Twenty patients (13 males and 7 females) with mandibular benign unilateral lesions were included, and divided into 2 groups. Group I consisted of 10 patients who underwent enucleation of the lesions followed by grafting of the bony defects with autologous bone marrow concentrates and CGF. Group II consisted of 10 patients who underwent enucleation of the lesions without grafting (control). Radiographic examinations were done immediately postoperative, then at 1, 3, 6, and 12 months, to evaluate the reduction in size and changes in bone density at the bony defects. Results indicated a significant increase in bone density with respect to the baseline levels in both groups (P < 0.05). The increase in bone density was significantly higher in group I compared with group II at the 6- and 12-month follow-up examinations (P < 0.05). The percent of reduction in the defects' size was significantly higher in group I compared with group II after 12 months (P = 0.00001). In conclusion, the clinical application of autologous bone marrow concentrates with CGF is a cost effective and safe biotechnology, which accelerates bone regeneration and improves the density of regenerated bone.

Modeling of Stiffness and Strength of Bone at Nanoscale.

PubMed

Abueidda, Diab W; Sabet, Fereshteh A; Jasiuk, Iwona M

2017-05-01

Two distinct geometrical models of bone at the nanoscale (collagen fibril and mineral platelets) are analyzed computationally. In the first model (model I), minerals are periodically distributed in a staggered manner in a collagen matrix while in the second model (model II), minerals form continuous layers outside the collagen fibril. Elastic modulus and strength of bone at the nanoscale, represented by these two models under longitudinal tensile loading, are studied using a finite element (FE) software abaqus. The analysis employs a traction-separation law (cohesive surface modeling) at various interfaces in the models to account for interfacial delaminations. Plane stress, plane strain, and axisymmetric versions of the two models are considered. Model II is found to have a higher stiffness than model I for all cases. For strength, the two models alternate the superiority of performance depending on the inputs and assumptions used. For model II, the axisymmetric case gives higher results than the plane stress and plane strain cases while an opposite trend is observed for model I. For axisymmetric case, model II shows greater strength and stiffness compared to model I. The collagen-mineral arrangement of bone at nanoscale forms a basic building block of bone. Thus, knowledge of its mechanical properties is of high scientific and clinical interests.

21 CFR 888.3565 - Knee joint patellofemorotibial metal/polymer porous-coated uncemented prosthesis.

Code of Federal Regulations, 2011 CFR

2011-04-01

... type of device is designed to achieve biological fixation to bone without the use of bone cement. This... bearing is rigidly secured to the metal tibial base plate. (b) Classification. Class II (special controls). The special control is FDA's guidance: “Class II Special Controls Guidance Document: Knee Joint...

Conditional expression of constitutively active estrogen receptor {alpha} in chondrocytes impairs longitudinal bone growth in mice

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

Ikeda, Kazuhiro; Tsukui, Tohru; Imazawa, Yukiko

2012-09-07

Highlights: Black-Right-Pointing-Pointer Conditional transgenic mice expressing constitutively active estrogen receptor {alpha} (caER{alpha}) in chondrocytes were developed. Black-Right-Pointing-Pointer Expression of caER{alpha} in chondrocytes impaired longitudinal bone growth in mice. Black-Right-Pointing-Pointer caER{alpha} affects chondrocyte proliferation and differentiation. Black-Right-Pointing-Pointer This mouse model is useful for understanding the physiological role of ER{alpha}in vivo. -- Abstract: Estrogen plays important roles in the regulation of chondrocyte proliferation and differentiation, which are essential steps for longitudinal bone growth; however, the mechanisms of estrogen action on chondrocytes have not been fully elucidated. In the present study, we generated conditional transgenic mice, designated as caER{alpha}{sup ColII}, expressing constitutively activemore » mutant estrogen receptor (ER) {alpha} in chondrocytes, using the chondrocyte-specific type II collagen promoter-driven Cre transgenic mice. caER{alpha}{sup ColII} mice showed retardation in longitudinal growth, with short bone lengths. BrdU labeling showed reduced proliferation of hypertrophic chondrocytes in the proliferating layer of the growth plate of tibia in caER{alpha}{sup ColII} mice. In situ hybridization analysis of type X collagen revealed that the maturation of hypertrophic chondrocytes was impaired in caER{alpha}{sup ColII} mice. These results suggest that ER{alpha} is a critical regulator of chondrocyte proliferation and maturation during skeletal development, mediating longitudinal bone growth in vivo.« less

Recombinant human basic fibroblast growth factor (bFGF) stimulates periodontal regeneration in class II furcation defects created in beagle dogs.

PubMed

Murakami, S; Takayama, S; Kitamura, M; Shimabukuro, Y; Yanagi, K; Ikezawa, K; Saho, T; Nozaki, T; Okada, H

2003-02-01

Several growth factors (or cytokines) have been recently investigated for their use as potential therapeutics for periodontal tissue regeneration. The objective of this study was to evaluate periodontal tissue regeneration, including new bone and cementum formation, following topical application of recombinant basic fibroblast growth factor (bFGF, FGF-2) to furcation class II defects. Twelve furcation class II bone defects were surgically created in six beagle dogs, then recombinant bFGF (30 micro g/site) + gelatinous carrier was topically applied to the bony defects. Six weeks after application, periodontal regeneration was analyzed. In all sites where bFGF was applied, periodontal ligament formation with new cementum deposits and new bone formation was observed histomorphometrically, in amounts greater than in the control sites. Basic FGF-applied sites exhibited significant regeneration as represented by the new bone formation rate (NBR) (83.6 +/- 14.3%), new trabecular bone formation rate (NTBR) (44.1 +/- 9.5%), and new cementum formation rate (NCR) (97.0 +/- 7.5%). In contrast, in the carrier-only sites, the NBR, NTBR, and NCR were 35.4 +/- 8.9%, 16.6 +/- 6.2%, and 37.2 +/- 15.1%, respectively. Moreover, no instances of epithelial down growth, ankylosis, or root resorption were observed in the bFGF-applied sites examined. The present results indicate that topical application of bFGF can enhance considerable periodontal regeneration in artificially created furcation class II bone defects of beagle dogs.

HLA-typing analysis following allogeneic bone grafting for sinus lifting.

PubMed

Piaia, Marcelo; Bub, Carolina Bonet; Succi, Guilherme de Menezes; Torres, Margareth; Costa, Thiago Henrique; Pinheiro, Fabricio Costa; Napimoga, Marcelo Henrique

2017-03-01

According to the Brazilian Association of Organ Transplants, in 2015, 19,408 bone transplants were performed in Brazil, over 90% by Dental Surgeons. The surgical technique itself has a respectable number of reports regarding its clinical efficacy, as measured by long-term survival of dental implants in grafted areas. Uncertainty remains, however, as to whether fresh frozen grafts from human bone donors remain immunologically innocuous in the body of the host. Six male with no previous medical history of note, including systemic diseases, surgery or blood transfusion were selected. These patients underwent reconstructive procedures (sinus lifting) using fresh frozen human bone from a tissue bank. All patients had venous blood samples collected prior to surgery and 6 months after the procedure. Anti-HLA analysis for the detection of HLA (human leukocyte antigen) antibodies was performed using methods such as the LABScreen PRA Class I and Class II, LABScreen Single Antigen Class I and Class II, Luminex Platform. Reactive individuals to the screening tests (LABScreen PRA) were further investigated to determine the specificity of the antibodies detected (LABScreen Single Antigen) with a cutoff value of median fluorescence intensity ≥500. As a result, it was observed that two patients (33%) were positive in screening tests, one presenting with anti-HLA Class I and II sensitization and the other with anti-HLA class II. The specificity analysis showed that the patients sensitized to HLA class II presented 4 specificities, 3 of which immunologically relevant. In the second individual, 23 specificities were identified, 6 of which immunologically important for HLA class I and 4 specificities for HLA class II, 3 of these were immunologically important. All specificities detected had average fluorescence. These findings are suggestive that sinus-lifting procedures with allogeneic bone can induce immunological sensitization.

Characterizing the Lower Paleolithic bone industry from Schöningen 12 II: A multi-proxy study.

PubMed

Julien, Marie-Anne; Hardy, Bruce; Stahlschmidt, Mareike C; Urban, Brigitte; Serangeli, Jordi; Conard, Nicholas J

2015-12-01

Although preservation of Paleolithic faunal assemblages from open-air settings is often poor, the Lower Paleolithic sites of Schöningen provide exceptionally well-preserved mammalian faunal material for investigating hominin/animal relationships. Pleistocene fossil assemblages, however, usually reflect a complex taphonomic history in which natural and anthropogenic processes are often superimposed. A number of examples of osseous finds that resemble tools were recently discovered in the MIS 9 deposits of Schöningen 12 II. Non-anthropogenic agents are known to produce surface modifications mimicking human artifacts and the identification of osseous remains used and/or deliberately modified by ancient hominins is often controversial in such old contexts. Multiple lines of evidence are thus useful for distinguishing between osseous artifacts and "eco-facts". In this paper, the recognition of the use of bone for different technological purposes by late Middle Pleistocene hominins is addressed through a multi-proxy study combining geoarcheology, bone taphonomy, zooarcheology, and use-wear analysis. This allowed the identification of the processes and agents responsible for the formation and modification of the different bone assemblages of Schöningen 12 II. Our analysis points to different types of bones having been likely used as tools. These results expand the diversity of the organic technological repertoire of the Middle Pleistocene hominins, making Schöningen 12 II a remarkable new source of information on osseous technology long before the Upper Paleolithic, the period traditionally viewed as the start of the systematic use of bone tools. Together with other observations of bone tools documented during the Lower and Middle Paleolithic, the results from Schöningen show that archeologists may have underestimated the diversity and importance of osseous technology among archaic hominins. Copyright © 2015 Elsevier Ltd. All rights reserved.

Press-fit acetabular cup fixation: principles and testing.

PubMed

Macdonald, W; Carlsson, L V; Charnley, G J; Jacobsson, C M

1999-01-01

Pre-clinical testing of the fixation of press-fit acetabular components of total hip prostheses relies on cadaver or synthetic bone, but the properties and geometry of bone models differ from those of physiological bone. Cup designs use varied mechanisms for initial stability in bone; therefore, using different analogues and tests is appropriate. Press-fit cup stability was tested in the following: firstly, polyurethane (PU) foam modelling cancellous support; secondly, glass-fibre reinforced epoxide (GFRE) tubes modelling acetabular cortical support; thirdly, cadaveric acetabula. Three commercial cups [Harris-Galante II (H-G-II), Zimmer; Optifix, Smith & Nephew, Richards; porous coated anatomic (PCA), Howmedica] and an experimental cup with enhanced rim fixation were tested in three modes: direct pull-out, lever-out and axial torque. The fixation stabilities measured in the PU and the GFRE models showed trends consistent with those in cadaver bone, differing in the oversizing and cup geometry. The experimental cup was significantly more secure in most modes than other cups; the H-G II and Optifix cups showed similar stabilities, lower than that of the experimental cup but greater than that of the PCA cup (analysis of variance and Tukey's highly significant test; p < 0.001). The stabilities measured in cadaver bone more closely approximated those in GFRE. The use of several bone analogues enables separation of fixation mechanisms, allowing more accurate prediction of in vivo performance.

A variant microcephalic osteodysplastic slender-bone disorder with growth hormone deficiency and a pigmentary retinopathy.

PubMed

Maclean, K; Ambler, G; Flaherty, M; Kozlowski, K; Adès, L C

2002-10-01

We present the case of a 3-year-old boy with post-natal growth failure, microcephaly, developmental delay, facial dysmorphism, an evolving pigmentary retinopathy, pituitary hypoplasia, micropenis, and growth hormone (GH) deficiency. He has a microcephalic osteodysplastic slender-bone disorder with disharmonic delayed osseous maturation, most closely resembling patients with microcephalic osteodysplastic primordial dwarfism type II (MOPD II). Intrauterine growth retardation, a universal finding in the MOPD II, was absent in our patient.

21 CFR 888.3150 - Elbow joint metal/polymer constrained cemented prosthesis.

Code of Federal Regulations, 2010 CFR

2010-04-01

... use with bone cement (§ 888.3027). (b) Classification. Class II. The special controls for this device...) “Guidance Document for Testing Orthopedic Implants with Modified Metallic Surfaces Apposing Bone or Bone... Biomaterials (Nonporous) for Surgical Implant with Respect to Effect of Material on Muscle and Bone,” (v) F...

21 CFR 888.3150 - Elbow joint metal/polymer constrained cemented prosthesis.

Code of Federal Regulations, 2012 CFR

2012-04-01

... use with bone cement (§ 888.3027). (b) Classification. Class II. The special controls for this device...) “Guidance Document for Testing Orthopedic Implants with Modified Metallic Surfaces Apposing Bone or Bone... Biomaterials (Nonporous) for Surgical Implant with Respect to Effect of Material on Muscle and Bone,” (v) F...

21 CFR 888.3150 - Elbow joint metal/polymer constrained cemented prosthesis.

Code of Federal Regulations, 2014 CFR

2014-04-01

... use with bone cement (§ 888.3027). (b) Classification. Class II. The special controls for this device...) “Guidance Document for Testing Orthopedic Implants with Modified Metallic Surfaces Apposing Bone or Bone... Biomaterials (Nonporous) for Surgical Implant with Respect to Effect of Material on Muscle and Bone,” (v) F...

21 CFR 888.3150 - Elbow joint metal/polymer constrained cemented prosthesis.

Code of Federal Regulations, 2013 CFR

2013-04-01

... use with bone cement (§ 888.3027). (b) Classification. Class II. The special controls for this device...) “Guidance Document for Testing Orthopedic Implants with Modified Metallic Surfaces Apposing Bone or Bone... Biomaterials (Nonporous) for Surgical Implant with Respect to Effect of Material on Muscle and Bone,” (v) F...

21 CFR 888.3150 - Elbow joint metal/polymer constrained cemented prosthesis.

Code of Federal Regulations, 2011 CFR

2011-04-01

... use with bone cement (§ 888.3027). (b) Classification. Class II. The special controls for this device...) “Guidance Document for Testing Orthopedic Implants with Modified Metallic Surfaces Apposing Bone or Bone... Biomaterials (Nonporous) for Surgical Implant with Respect to Effect of Material on Muscle and Bone,” (v) F...

Bone alterations are associated with ankle osteoarthritis joint pain

PubMed Central

Nakamura, Yukio; Uchiyama, Shigeharu; Kamimura, Mikio; Komatsu, Masatoshi; Ikegami, Shota; Kato, Hiroyuki

2016-01-01

The etiology of ankle osteoarthritis (OA) is largely unknown. We analyzed 24 ankle OA of 21 patients diagnosed by plain radiographs using magnetic resonance imaging (MRI). Ankle joint pain disappeared in 22 out of 24 joints by conservative treatment. MRI bone signal changes in and around the ankle joints were observed in 22 of 24 joints. Bone signal changes along the joint line were seen in 10 of 11 joints as a Kellgren-Lawrence (KL) grade of II to IV. Such signal changes were witnessed in only 4 of 13 joints with KL grade 0 or I. In the talocrural joint, bone alterations occurred in both tibia and talus bones through the joint line in cases of KL grade III or IV, while focal bone alterations were present in the talus only in KL grade I or II cases. Sixteen of 24 joints exhibited intraosseous bone signal changes, which tended to correspond to joint pain of any ankle OA stage. Our results suggest that bone alterations around the ankle joint might be one of the etiologies of OA and associated with ankle joint pain. PMID:26776564

Bone alterations are associated with ankle osteoarthritis joint pain.

PubMed

Nakamura, Yukio; Uchiyama, Shigeharu; Kamimura, Mikio; Komatsu, Masatoshi; Ikegami, Shota; Kato, Hiroyuki

2016-01-18

The etiology of ankle osteoarthritis (OA) is largely unknown. We analyzed 24 ankle OA of 21 patients diagnosed by plain radiographs using magnetic resonance imaging (MRI). Ankle joint pain disappeared in 22 out of 24 joints by conservative treatment. MRI bone signal changes in and around the ankle joints were observed in 22 of 24 joints. Bone signal changes along the joint line were seen in 10 of 11 joints as a Kellgren-Lawrence (KL) grade of II to IV. Such signal changes were witnessed in only 4 of 13 joints with KL grade 0 or I. In the talocrural joint, bone alterations occurred in both tibia and talus bones through the joint line in cases of KL grade III or IV, while focal bone alterations were present in the talus only in KL grade I or II cases. Sixteen of 24 joints exhibited intraosseous bone signal changes, which tended to correspond to joint pain of any ankle OA stage. Our results suggest that bone alterations around the ankle joint might be one of the etiologies of OA and associated with ankle joint pain.

Insulin-Like Growth Factor Regulates Peak Bone Mineral Density in Mice by Both Growth Hormone-Dependent and -Independent Mechanisms

PubMed Central

Mohan, Subburaman; Richman, Charmaine; Guo, Rongqing; Amaar, Yousef; Donahue, Leah Rea; Wergedal, Jon; Baylink, David J.

2010-01-01

To evaluate the relative contribution of the GH/IGF axis to the development of peak bone mineral density (BMD), we measured skeletal changes in IGF-I knockout (KO), IGF-II KO, and GH-deficient lit/lit mice and their corresponding control mice at d 23 (prepubertal), 31 (pubertal), and 56 (postpubertal) in the entire femur by dual energy x-ray absorptiometry and in the mid-diaphysis by peripheral quantitative computed tomography. Lack of growth factors resulted in different degrees of failure of skeletal growth depending on the growth period and the growth factor involved. At d 23, femoral length, size, and BMD were reduced by 25–40%, 15–17%, and 8–10%, respectively, in mice deficient in IGF-I, IGF-II, and GH compared with the control mice. During puberty, BMD increased by 40% in control mice and by 15% in IGF-II KO and GH-deficient mice, whereas it did not increase in the IGF-I KO mice. Disruption of IGF-I, but not IGF-II, completely prevented the periosteal expansion that occurs during puberty, whereas it was reduced by 50% in GH-deficient mice. At d 56, femoral length, size, and BMD were reduced by 40–55%, 11–18%, and 25–32%, respectively, in mice deficient in IGF-I, IGF-II, and GH compared with the control mice. Our data demonstrate that: 1) mice deficient in IGF-I exhibit a greater impairment in bone accretion than mice deficient in IGF-II or GH; 2) GH/IGF-I, but not IGF-II, is critical for puberty-induced bone growth; and 3) IGF-I effects on bone accretion during prepuberty are mediated predominantly via mechanisms independent of GH, whereas during puberty they are mediated via both GH-dependent and GH-independent mechanisms. PMID:12586770

An evaluation of bone scans as screening procedures for occult metastases in primary breast cancer.

PubMed Central

Baker, R R; Holmes, E R; Alderson, P O; Khouri, N F; Wagner, H N

1977-01-01

Preoperative bone scans were obtained in 104 patients with operable breast cancer. Areas of increased radioactivity detected by the bone scan were correlated with appropriate radiographs. One of 64 patients (1.5%) with clinical Stage I and Stage II breast cancer had a metastatic lesion detected by the preoperative bone scan. In contrast, 10 of 41 patients (24%) with Stage III breast cancer had occult metastatic lesions detected by the preoperative bone scan. The majority of patients with abnormal bone scans and no radiographic evidence of a benign lesion to explain the cause of the increased radioactivity proved to have metastatic breast cancer on follow-examination. Even though 20% of patients with operable breast cancer will eventually develop bone metastases, our results indicate that preoperative bone scans are not an effective means of predicting which patients with Stage I and Stage II disease will develop metastatic breast cancer. Because of the considerably increased frequency of detection of occult metastases in patients with Stage III breast cancer, bone scans should be obtained routinely in the preoperative assessment of these patients. Images Figs. 1a and b. Figs. 2a and b. Figs. 3a-d. PMID:889378

A Novel M2e Based Flu Vaccine Formulation for Dogs

PubMed Central

Leclerc, Denis; Rivest, Marie; Babin, Cindy; López-Macias, Constantino; Savard, Pierre

2013-01-01

Background The USA 2004 influenza virus outbreak H3N8 in dogs heralded the emergence of a new disease in this species. A new inactivated H3N8 vaccine was developed to control the spread of the disease but, as in humans and swine, it is anticipated that the virus will mutate shift and drift in the dog population. Therefore, there is a need for a vaccine that can trigger a broad protection to prevent the spread of the virus and the emergence of new strains. Methodology and Principal Findings The universal M2e peptide is identical in almost all the H3N8 influenza strains sequenced to date and known to infect dogs. This epitope is therefore a good choice for development of a vaccine to provide broad protection. Malva mosaic virus (MaMV) nanoparticles were chosen as a vaccine platform to improve the stability of the M2e peptide and increase its immunogenicity in animals. The addition of an adjuvant (OmpC) purified from Salmonella typhi membrane in the vaccine formulation increased the immune response directed to the M2e peptide significantly and enlarged the protection to include the heterosubtypic strain of influenza in a mouse model. An optimal vaccine formulation was also shown to be immunogenic in dogs. Conclusions and Significance The MaMV vaccine platform triggered an improved immune response directed towards the universal M2e peptide. The adjuvant OmpC increased the immune response to the M2e peptide and protection to a heterosubtypic influenza strain that harbors a different M2e peptide in a mouse model. Antibodies generated by the vaccine formulation showed cross-reactivity with M2e peptides derived from influenza strains H9N2, H5N1 and H1N1. The vaccine formulation shows a potential for commercialization of a new M2e based vaccine in dogs. PMID:24098576

Immunogenicity in chickens with orally administered recombinant chicken-borne Lactobacillus saerimneri expressing FimA and OmpC antigen of O78 avian pathogenic Escherichia coli.

PubMed

Ma, Sun-Ting; Ding, Guo-Jie; Huang, Xue-Wei; Wang, Zi-Wei; Wang, Li; Yu, Mei-Ling; Shi, Wen; Jiang, Yan-Ping; Tang, Li-Jie; Xu, Yi-Gang; Li, Yi-Jing

2018-03-01

Avian colibacillosis is responsible for economic losses to poultry producers worldwide. To combat this, we aimed to develop an effective oral vaccine for chicken against O78 avian pathogenic Escherichia coli (APEC) infection through a Lactobacillus delivery system. Eight Lactobacillus strains isolated from the intestines of broiler chickens were evaluated based on their in vitro adherence ability to assess their potential as a delivery vector. Fimbrial subunit A (FimA) and outer-membrane protein C (OmpC) of APEC with and without fusion to dendritic cell-targeting peptide (DCpep) and microfold cell-targeting peptide (Co1) were displayed on the surface of Lactobacillus saerimneri M-11 and yielded vaccine groups (pPG-ompC-fimA/M-11 and pPG-ompC-fimA-Co1-DCpep/M-11, respectively). The colonization of the recombinant strains in vivo was assessed and the immunogenicity and protective efficacy of orally administered recombinant strains in chickens were evaluated. The colonization of the recombinant strains in vivo revealed no significant differences between the recombinant and wild-type strains. Chickens orally administered with vaccine groups showed significantly higher levels of OmpC/FimA-specific IgG in serum and mucosal IgA in cecum lavage, nasal lavage and stool compared to the pPG/M-11 group. After challenge with APEC CVCC1553, better protective efficacy was observed in chickens orally immunized with pPG-ompC-fimA/M-11 and pPG-ompC-fimA-Co1-DCpep/M-11, but no significant differences were observed between the two groups. Recombinant chicken-borne L. saerimneri M-11 showed good immunogenicity in chickens, suggesting that it may be a promising vaccine candidate against APEC infections. However, the activity of mammalian DCpep and Co1 was not significant in chickens.

ACE-2/Ang1-7/Mas cascade mediates ACE inhibitor, captopril, protective effects in estrogen-deficient osteoporotic rats.

PubMed

Abuohashish, Hatem M; Ahmed, Mohammed M; Sabry, Dina; Khattab, Mahmoud M; Al-Rejaie, Salim S

2017-08-01

The local role of the renin angiotensin system (RAS) was documented recently beside its conventional systemic functions. Studies showed that the effector angiotensin II (AngII) alters bone health, while inhibition of the angiotensin converting enzyme (ACE-1) preserved these effects. The newly identified Ang1-7 exerts numerous beneficial effects opposing the AngII. Thus, the current study examines the role of Ang1-7 in mediating the osteo-preservative effects of ACEI (captopril) through the G-protein coupled Mas receptor using an ovariectomized (OVX) rat model of osteoporosis. 8 weeks after the surgical procedures, captopril was administered orally (40mgkg -1 d -1 ), while the specific Mas receptor blocker (A-779) was delivered at infusion rate of 400ngkg -1 min -1 for 6 weeks. Bone metabolic markers were measured in serum and urine. Minerals concentrations were quantified in serum, urine and femoral bones by inductive coupled plasma mass spectroscopy (ICP-MS). Trabecular and cortical morphometry was analyzed in the right distal femurs using micro-CT. Finally, the expressions of RAS peptides, enzymes and receptors along with the receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) were determined femurs heads. OVX animals markedly showed altered bone metabolism and mineralization along with disturbed bone micro-structure. Captopril significantly restored the metabolic bone bio-markers and corrected Ca 2+ and P values in urine and bones of estrogen deficient rats. Moreover, the trabecular and cortical morphometric features were repaired by captopril in OVX groups. Captopril also improved the expressions of ACE-2, Ang1-7, Mas and OPG, while abolished OVX-induced up-regulation of ACE-1, AngII, Ang type 1 receptor (AT1R) and RANKL. Inhibition of Ang1-7 cascade by A-779 significantly eradicated captopril protective effects on bone metabolism, mineralization and micro-structure. A-779 also restored OVX effects on RANKL expression and ACE-1/AngII/AT1R cascade and down-regulated OPG expression and ACE-2/Ang1-7/Mas pathway. In line with the clinical observations of the bone-preservative properties following ACE-1 inhibition, local activation of ACE-2/Ang1-7/Mas signaling and suppressed osteoclastogenesis seem responsible for the osteo-preservative effect of captopril, which could offers a potential therapeutic value in treatment of disabling bone and skeletal muscular diseases. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Growth factors and cytokines in patients with long bone fractures and associated spinal cord injury.

PubMed

Khallaf, Fathy G; Kehinde, Elijah O; Mostafa, Ahmed

2016-06-01

The aim of the study was to test the effect of acute traumatic spinal cord injury of quadriplegia or paraplegia on bone healing in patients with associated long bone fractures and to investigate the molecular and cellular events of the underlying mechanism for a possible acceleration. Healing indicators of long bone fractures and growth factors, IGF-II, platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), Activin-A, and cytokine I-L-1, in the patients' blood were calculated and measured for 21 patients with spinal cord injuries and associated long bone fractures in prospective controlled study and compared to 20 patients with only spinal cord injuries, 30 patients with only long bone fractures, and 30 healthy volunteers. The study results showed that long bone fractures in patients with associated acute traumatic spinal cord injury of quadriplegia or paraplegia heal more expectedly, faster, and with exuberant florid union callus (P > 0.001) and show statistically significant higher levels of growth factors like PDGF, VEGF, Activin-A, and cytokine I-L-1, along the 3 weeks of follow-up (P > 0.005). I-IGF-II showed statistically significant subnormal level along the whole follow-up period in the same patients (P > 0.005). We concluded that long bone fractures in spinal cord injury patients heal more expectedly, faster, and with exuberant and florid callus formation; growth factors like IGF-II, PDGF, VEGF, Activin-A, and cytokine I-L-I have roles as mediators, in molecular events and as byproducts of the subtle mechanism of accelerated osteogenesis in these patients and may represent therapeutic potentials to serve as agents to enhance bone repair.

Systemically administered rhBMP-2 promotes MSC activity and reverses bone and cartilage loss in osteopenic mice.

PubMed

Turgeman, Gadi; Zilberman, Yoram; Zhou, Shuanhu; Kelly, Pam; Moutsatsos, Ioannis K; Kharode, Yogendra P; Borella, Luis E; Bex, Frederick J; Komm, Barry S; Bodine, Peter V N; Gazit, Dan

2002-01-01

Osteoporosis is a disease manifested in drastic bone loss resulting in osteopenia and high risk for fractures. This disease is generally divided into two subtypes. The first, post-menopausal (type I) osteoporosis, is primarily related to estrogen deficiency. The second, senile (type II) osteoporosis, is mostly related to aging. Decreased bone formation, as well as increased bone resorption and turnover, are thought to play roles in the pathophysiology of both types of osteoporosis. In this study, we demonstrate in murine models for both type I (estrogen deficiency) and type II (senile) osteopenia/osteoporosis that reduced bone formation is related to a decrease in adult mesenchymal stem cell (AMSC) number, osteogenic activity, and proliferation. Decreased proliferation is coupled with increased apoptosis in AMSC cultures obtained from osteopenic mice. Recombinant human bone morphogenetic protein (rhBMP-2) is a highly osteoinductive protein, promoting osteogenic differentiation of AMSCs. Systemic intra-peritoneal (i.p.) injections of rhBMP-2 into osteopenic mice were able to reverse this phenotype in the bones of these animals. Moreover, this change in bone mass was coupled to an increase in AMSCs numbers, osteogenic activity, and proliferation as well as a decrease in apoptosis. Bone formation activity was increased as well. However, the magnitude of this response to rhBMP-2 varied among different stains of mice. In old osteopenic BALB/c male mice (type II osteoporosis model), rhBMP-2 systemic treatment also restored both articular and epiphyseal cartilage width to the levels seen in young mice. In summary, our study shows that AMSCs are a good target for systemically active anabolic compounds like rhBMP-2. Copyright 2002 Wiley-Liss, Inc.

Treatment of type II and type III open tibia fractures in children.

PubMed

Bartlett, C S; Weiner, L S; Yang, E C

1997-07-01

To determine whether severe open tibial fractures in children behave like similar fractures in adults. A combined retrospective and prospective review evaluated treatment protocol for type II and type III open tibial fractures in children over a ten-year period from 1984 to 1993. Twenty-three fractures were studied in children aged 3.5 to 14.5 (18 boys and 5 girls). There were six type II, eight type IIIA, and nine type IIIB fractures. Type I fractures were not included. Seven fractures were comminuted with significant butterfly fragments or segmental patterns. Treatment consisted of adequate debridement of soft tissues, closure of dead space, and stabilization with external fixation. Bone debridement only included contaminated devitalized bone or devitalized bone without soft tissue coverage. Bone that could be covered despite periosteal stripping was preserved. Clinical and roentgenographic examinations were used to determine time to union. All fractures in this series healed between eight and twenty-six weeks. Wound coverage included two flaps, three skin grafts, and two delayed primary closures. No bone grafts were required. There were no deep infections, growth arrests, or malunions. Follow-up has ranged from six months to four years. Open tibia fractures in children differ from similar fractures in adults in the following ways: soft tissues have excellent healing capacity, devitalized bone that is not contaminated or exposed can be saved and will become incorporated, and external fixation can be maintained until the fracture has healed. Periosteum in young children can form bone even in the face of bone loss.

Utility of bone scanning in detecting occult skeletal metastases from cervical carcinoma

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

Katz, R.D.; Alderson, P.O.; Rosenshein, N.B.

1979-11-01

Bone scans were obtained in 100 patients with carcinoma of the cervix in order to search for occult skeletal metastases. Scans revealed metastases in 4 patients with advanced stages of disease, but the scans in 79 patients with Stage 0, I, or II disease were negative. The scans in 14 patients showed renal asymmetry; 11 of these had obstructive uropathy due to tumor invasion or radiation therapy. Bone scanning does not seem warranted as a screening test in asymptomatic patients with Stage 0, I, or II carcinoma. If the test is done, renal symmetry should be carefully evaluated.

Decreased bone formation and increased osteoclastogenesis cause bone loss in mucolipidosis II

PubMed Central

Kollmann, Katrin; Pestka, Jan Malte; Kühn, Sonja Christin; Schöne, Elisabeth; Schweizer, Michaela; Karkmann, Kathrin; Otomo, Takanobu; Catala-Lehnen, Philip; Failla, Antonio Virgilio; Marshall, Robert Percy; Krause, Matthias; Santer, Rene; Amling, Michael; Braulke, Thomas; Schinke, Thorsten

2013-01-01

Mucolipidosis type II (MLII) is a severe multi-systemic genetic disorder caused by missorting of lysosomal proteins and the subsequent lysosomal storage of undegraded macromolecules. Although affected children develop disabling skeletal abnormalities, their pathogenesis is not understood. Here we report that MLII knock-in mice, recapitulating the human storage disease, are runted with accompanying growth plate widening, low trabecular bone mass and cortical porosity. Intralysosomal deficiency of numerous acid hydrolases results in accumulation of storage material in chondrocytes and osteoblasts, and impaired bone formation. In osteoclasts, no morphological or functional abnormalities are detected whereas osteoclastogenesis is dramatically increased in MLII mice. The high number of osteoclasts in MLII is associated with enhanced osteoblastic expression of the pro-osteoclastogenic cytokine interleukin-6, and pharmacological inhibition of bone resorption prevented the osteoporotic phenotype of MLII mice. Our findings show that progressive bone loss in MLII is due to the presence of dysfunctional osteoblasts combined with excessive osteoclastogenesis. They further underscore the importance of a deep skeletal phenotyping approach for other lysosomal diseases in which bone loss is a prominent feature. PMID:24127423

[Search for non-relative donor by the Russian register of bone marrow donors].

PubMed

Zaretskaia, Iu M; Khamaganova, E G; Aleshchenko, S M; Murashova, L A

2002-01-01

To select maximally HLA compatible donor for hematological patients who need transplantation of bone marrow from non-relative donor. 75 patients with hematological malignancy were observed. All of them have indications to non-relative transplantation of the bone marrow. Methods of polymerase chain reaction with sequence-specific primers and classic microlymphocytotoxic test were used. Typing of HLA antigens of class I and alleles of class II loci enabled search for non-relative donor for transplantation of bone marrow in accordance with the requirements of the European Federation of Immunogenetics. Most of the patients (86.6%) had at least one potential HLA-A, -B, -DR compatible donor. Half of the patients had potential donors typed at the allele level by class II loci. This diminishes time of HLA compatible donor selection. DNA typing enables the search for the non-relative donors meeting modern requirements. This allowed 5 non-relative bone marrow transplantations.

Effect of angiotensin II receptor blocker, olmesartan, on turnover of bone metabolism in bedridden elderly hypertensive women with disuse syndrome.

PubMed

Aoki, Motokuni; Kawahata, Hirohisa; Sotobayashi, Daisuke; Yu, Hisahiro; Moriguchi, Atsushi; Nakagami, Hironori; Ogihara, Toshio; Morishita, Ryuichi

2015-08-01

Although recent studies suggest that several antihypertensive drugs could reduce the risk of bone fracture, it is still unclear how these drugs act on bone remodeling, especially in elderly women with severe osteoporosis with disuse syndrome. In the present study, we investigated the effects of a calcium channel blocker (CCB) and an angiotensin II receptor blocker (ARB) on bone metabolism in elderly bedridden women with hypertension and disuse syndrome. Elderly bedridden women (aged >75 years) receiving antihypertensive therapy treated with CCB were recruited in the present study. The participants were divided into two groups--CCB group and ARB group--and followed up to 12 months. Markers of bone resorption were markedly increased, suggesting accelerated bone resorption in the participants of the present study. In the follow-up period, the patients treated with a CCB showed a significant decrease in bone mineral density in a time-dependent manner, accompanied by a significant increase in bone resorption markers, whereas treatment with olmesartan inhibited bone loss, associated with attenuation of increased bone resorption markers. Bone mineral density of femoral neck in the CCB group was significantly lower than that in the ARB group at 6 months. The present study showed inhibitory effects of an ARB on bone resorption in hypertensive patients with accelerated bone resorption, such as elderly bedridden women, and indicated an important role of the renin-angiotensin system in bone metabolism. In elderly hypertensive patients, ARB might be expected to have additional beneficial potential to maintain bone health in bedridden patients. © 2014 Japan Geriatrics Society.

A paradoxical presentation of rickets and secondary osteomyelitis of the jaw in Type II autosomal dominant osteopetrosis: Rare case reports.

PubMed

Jayachandran, S; Kumar, M Suresh

2016-01-01

Osteopetrosis is a rare genetic bone disorder arising due to a defect in the differentiation or function of osteoclast which results in a generalized increase in bone mass. Osteomyelitis is one of the most common complications because of decreased bone marrow function and compromised blood supply. Radiologist plays a vital role in diagnosing osteopetrosis. Here, we present two cases of autosomal dominant osteopetrosis Type II (ADO II) with secondary osteomyelitis changes which were reported to our department. One of these two cases presented with secondary osteomyelitis in both maxilla and mandible and features of rickets, which is very rarely seen in ADO II. To the best of our knowledge, the presentation of rickets with ADO is the first of its kind to be reported. In this paper, we describe the clinical and radiological features leading to the diagnosis of ADO in these two patients. Further, a review of the literature regarding ADO is discussed.

Roles of Osteonectin in Breast Cancer Metastasis to Bone

DTIC Science & Technology

2005-05-01

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

Positive modulator of bone morphogenic protein-2

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

Zamora, Paul O.; Pena, Louis A.; Lin, Xinhua

Compounds of the present invention of formula I and formula II are disclosed in the specification and wherein the compounds are modulators of Bone Morphogenic Protein activity. Compounds are synthetic peptides having a non-growth factor heparin binding region, a linker, and sequences that bind specifically to a receptor for Bone Morphogenic Protein. Uses of compounds of the present invention in the treatment of bone lesions, degenerative joint disease and to enhance bone formation are disclosed.

Positive modulator of bone morphogenic protein-2

DOEpatents

Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY; Takahashi, Kazuyuki [Germantown, MD

2009-01-27

Compounds of the present invention of formula I and formula II are disclosed in the specification and wherein the compounds are modulators of Bone Morphogenic Protein activity. Compounds are synthetic peptides having a non-growth factor heparin binding region, a linker, and sequences that bind specifically to a receptor for Bone Morphogenic Protein. Uses of compounds of the present invention in the treatment of bone lesions, degenerative joint disease and to enhance bone formation are disclosed.

21 CFR 872.4600 - Intraoral ligature and wire lock.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) Identification. An intraoral ligature and wire lock is a metal device intended to constrict fractured bone segments in the oral cavity. The bone segments are stabilized by wrapping the ligature (wire) around the fractured bone segments and locking the ends together. (b) Classification. Class II. ...

21 CFR 872.4600 - Intraoral ligature and wire lock.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) Identification. An intraoral ligature and wire lock is a metal device intended to constrict fractured bone segments in the oral cavity. The bone segments are stabilized by wrapping the ligature (wire) around the fractured bone segments and locking the ends together. (b) Classification. Class II. ...

21 CFR 872.4600 - Intraoral ligature and wire lock.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) Identification. An intraoral ligature and wire lock is a metal device intended to constrict fractured bone segments in the oral cavity. The bone segments are stabilized by wrapping the ligature (wire) around the fractured bone segments and locking the ends together. (b) Classification. Class II. ...

21 CFR 872.4600 - Intraoral ligature and wire lock.

Code of Federal Regulations, 2012 CFR

2012-04-01

...) Identification. An intraoral ligature and wire lock is a metal device intended to constrict fractured bone segments in the oral cavity. The bone segments are stabilized by wrapping the ligature (wire) around the fractured bone segments and locking the ends together. (b) Classification. Class II. ...

21 CFR 872.4600 - Intraoral ligature and wire lock.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) Identification. An intraoral ligature and wire lock is a metal device intended to constrict fractured bone segments in the oral cavity. The bone segments are stabilized by wrapping the ligature (wire) around the fractured bone segments and locking the ends together. (b) Classification. Class II. ...

Evaluation of Bone Thickness and Density in the Lower Incisors' Region in Adults with Different Types of Skeletal Malocclusion using Cone-beam Computed Tomography.

PubMed

Al-Masri, Maram M N; Ajaj, Mowaffak A; Hajeer, Mohammad Y; Al-Eed, Muataz S

2015-08-01

To evaluate the bone thickness and density in the lower incisors' region in orthodontically untreated adults, and to examine any possible relationship between thickness and density in different skeletal patterns using cone-beam computed tomography (CBCT). The CBCT records of 48 patients were obtained from the archive of orthodontic department comprising three groups of malocclusion (class I, II and III) with 16 patients in each group. Using OnDemand 3D software, sagittal sections were made for each lower incisor. Thicknesses and densities were measured at three levels of the root (cervical, middle and apical regions) from the labial and lingual sides. Accuracy and reliability tests were undertaken to assess the intraobserver reliability and to detect systematic error. Pearson correlation coefficients were calculated and one-way analysis of variance (ANOVA) was employed to detect significant differences among the three groups of skeletal malocclusion. Apical buccal thickness (ABT) in the four incisors was higher in class II and I patients than in class III patients (p < 0.05). There were significant differences between buccal and lingual surfaces at the apical and middle regions only in class II and III patients. Statistical differences were found between class I and II patients for the cervical buccal density (CBD) and between class II and III patients for apical buccal density (ABD). Relationship between bone thickness and density values ranged from strong at the cervical regions to weak at the apical regions. Sagittal skeletal patterns affect apical bone thickness and density at buccal surfaces of the four lower incisors' roots. Alveolar bone thickness and density increased from the cervical to the apical regions.

Mechanical induction of critically delayed bone healing in sheep: radiological and biomechanical results.

PubMed

Schell, Hanna; Thompson, Mark S; Bail, Hermann J; Hoffmann, Jan-Erik; Schill, Alexander; Duda, Georg N; Lienau, Jasmin

2008-10-20

This study aimed to mechanically produce a standardized ovine model for a critically delayed bone union. A tibial osteotomy was stabilized with either a rigid (group I) or mechanically critical (group II) external fixator in sheep. Interfragmentary movements and ground reaction forces were monitored throughout the healing period of 9 weeks. After sacrifice at 6 weeks, 9 weeks and 6 months, radiographs were taken and the tibiae were examined mechanically. Interfragmentary movements were considerably larger in group II throughout the healing period. Unlike group I, the operated limb in group II did not return to full weight bearing during the treatment period. Radiographic and mechanical observations showed significantly inferior bone healing in group II at 6 and 9 weeks compared to group I. After 6 months, five sheep treated with the critical fixator showed radiological bridging of the osteotomy, but the biomechanical strength of the repair was still inferior to group I at 9 weeks. The remaining three animals had even developed a hypertrophic non-union. In this study, mechanical instability was employed to induce a critically delayed healing model in sheep. In some cases, this approach even led to the development of a hypertrophic non-union. The mechanical induction of critical bone healing using an external fixation device is a reasonable attempt to investigate the patho-physiological healing cascade without suffering from any biological intervention. Therefore, the presented ovine model provides the basis for a comparative evaluation of mechanisms controlling delayed and standard bone healing.

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

PubMed Central

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

2013-01-01

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

Characterizing the inorganic/organic interface in cancer bone metastasis

NASA Astrophysics Data System (ADS)

Wu, Fei

Bone metastasis frequently occurs in patients with advanced breast cancer and remains a major source of mortality. At the molecular level, bone is a nanocomposite composed of inorganic bone mineral deposited within an organic extracellular matrix (ECM). Although the exact mechanisms of bone metastasis remain unclear, the nanoscale materials properties of bone mineral have been implicated in this process. Bone apatite is closely related to synthetic hydroxyapatite (HAP, Ca10(PO4)6(OH)2) in terms of structural and mechanical properties. Additionally, although the primary protein content of bone is collagen I, the glycoprotein fibronectin (Fn) is essential in maintaining the overall integrity of the bone matrix. Importantly, in vivo, neither breast cancer cells nor normal bone cells interact directly with the bone mineral but rather with the protein film adsorbed onto the mineral surface. Therefore, we hypothesized that breast cancer cell functions were regulated by differential fibronectin adsorption onto hydroxyapatite, which led to pathological remodeling of the bone matrix and sustained bone metastasis. Three model systems containing HAP and Fn were developed for this thesis. In model system I, a library of synthetic HAP nanoparticles were utilized to investigate the effect of mineral size, shape, and crystallinity on Fn conformation, using Forster resonance energy transfer (FRET) spectroscopy. In model system II, Fn-functionalized large geologic HAP crystals were used instead of HAP nanoparticles to avoid cellular uptake when investigating subsequent cell functions. Overall our FRET analysis (models I and II) revealed that Fn conformation depended on size, surface chemistry, and roughness of underlying HAP. When breast cancer cells were seeded on the Fn-coated HAP crystal facets (model II), our data indicated high secretion levels of proangiogenic and proinflammatory factors associated with the presence of unfolded Fn conformations, likely caused by differential engagement of cell receptors integrins with the underlying Fn. Finally, in model system III, Fn fibrillar structures (mimicking the bone matrix) were fabricated and characterized in presence of HAP nanoparticles, suggesting that the presence of microcalcifications found in tumorous/inflammed tissues affects both the structural and mechanical properties of the surrounding ECM. Collectively, our study of cellular behavior regulated by mineral/ECM interactions provides insights into the pathogenesis of breast cancer bone metastasis as well as other HAP-related inflammation.

Kartogenin with PRP promotes the formation of fibrocartilage zone in the tendon-bone interface.

PubMed

Zhou, Yiqin; Zhang, Jianying; Yang, Jinsong; Narava, Manoj; Zhao, Guangyi; Yuan, Ting; Wu, Haishan; Zheng, Nigel; Hogan, MaCalus V; Wang, James H-C

2017-12-01

Treatment of tendon-bone junction injuries is a challenge because tendon-bone interface often heals poorly and the fibrocartilage zone, which reduces stress concentration, at the interface is not formed. In this study, we used a compound called kartogenin (KGN) with platelet-rich plasma (PRP) to induce the formation of fibrocartilage zone in a rat tendon graft-bone tunnel model. The experimental rats received KGN-PRP or PRP injections in the tendon graft-bone tunnel interface. The control group received saline. After 4, 8 and 12 weeks, Safranin O staining of the tendon graft-bone tunnels revealed abundant proteoglycans in the KGN-PRP group indicating the formation of cartilage-like transition zone. Immunohistochemical and immuno-fluorescence staining revealed collagen types I (Col-I) and II (Col-II) in the newly formed fibrocartilage zone. Both fibrocartilage zone formation and maturation were healing time dependent. In contrast, the PRP and saline control groups had no cartilage-like tissues and minimal Col-I and Col-II staining. Some gaps were also present in the saline control group. Finally, pull-out strength in the KGN-PRP-treated group at 8 weeks was 1.4-fold higher than the PRP-treated group and 1.6-fold higher than the saline control group. These findings indicate that KGN, with PRP as a carrier, promotes the formation of fibrocartilage zone between the tendon graft and bone interface. Thus, KGN-PRP may be used as a convenient cell-free therapy in clinics to promote fibrocartilage zone formation in rotator calf repair and anterior cruciate ligament reconstruction, thereby enhancing the mechanical strength of the tendon-bone interface and hence the clinical outcome of these procedures. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Human mesenchymal stem cells and biomaterials interaction: a promising synergy to improve spine fusion.

PubMed

Barbanti Brodano, G; Mazzoni, E; Tognon, M; Griffoni, C; Manfrini, M

2012-05-01

Spine fusion is the gold standard treatment in degenerative and traumatic spine diseases. The bone regenerative medicine needs (i) in vitro functionally active osteoblasts, and/or (ii) the in vivo induction of the tissue. The bone tissue engineering seems to be a very promising approach for the effectiveness of orthopedic surgical procedures, clinical applications are often hampered by the limited availability of bone allograft or substitutes. New biomaterials have been recently developed for the orthopedic applications. The main characteristics of these scaffolds are the ability to induce the bone tissue formation by generating an appropriate environment for (i) the cell growth and (ii) recruiting precursor bone cells for the proliferation and differentiation. A new prototype of biomaterials known as "bioceramics" may own these features. Bioceramics are bone substitutes mainly composed of calcium and phosphate complex salt derivatives. In this study, the characteristics bioceramics bone substitutes have been tested with human mesenchymal stem cells obtained from the bone marrow of adult orthopedic patients. These cellular models can be employed to characterize in vitro the behavior of different biomaterials, which are used as bone void fillers or three-dimensional scaffolds. Human mesenchymal stem cells in combination with biomaterials seem to be good alternative to the autologous or allogenic bone fusion in spine surgery. The cellular model used in our study is a useful tool for investigating cytocompatibility and biological features of HA-derived scaffolds.

21 CFR 882.5900 - Preformed craniosynostosis strip.

Code of Federal Regulations, 2010 CFR

2010-04-01

... bone edges of craniectomy sites (sites where the skull has been cut) to prevent the bone from regrowing in patients whose skull sutures are abnormally fused together. (b) Classification. Class II...

[Pedicled vascularized bone grafts from the dorsum of the distal radius for treatment of scaphoid nonunions].

PubMed

Sauerbier, Michael; Bishop, Allen T; Ofer, Nina

2009-11-01

Bony healing and reconstruction of the scaphoid with use of a reverse-flow pedicle vascularized bone graft from the dorsal aspect of the distal radius. Revitalization of the proximal fragment in case of avascular necrosis. Scaphoid nonunion, especially of the proximal pole. Nonunion after failed attempts of autogenous nonvascularized bone grafting. Avascular necrosis of the scaphoid (Preiser's disease). Avascular osteonecrosis of other carpal bones (i.e., Kienböck's disease stage II and IIIa). However, these will not be addressed in this paper. Advance carpal collapse (SNAC [scaphoid nonunion advanced collapse] wrist stage II and III). Avascular necrosis with broken proximal pole of the scaphoid. Malformation, disease or previous injury of the vascular system. Reconstruction of the scaphoid by interposition of a vascularized bone graft from the dorsum of the distal radius, where several vascularized bone grafts can be harvested, and fixation by a scaphoid screw. Management Immobilization for 6 weeks in a forearm cast including the first phalanx of the thumb. 48 scaphoid nonunions were treated with 1,2-ICSRA-based (intercompartmental supraretinacular artery) vascularized bone grafts: 34 scaphoid nonunions went on to union at an average of 15.6 weeks after surgery.

75 FR 43533 - Medicare Program; Meeting of the Medicare Evidence Development and Coverage Advisory Committee...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-26

... and off-label use of bone morphogenetic proteins (BMPs). This meeting is open to the public in... use of bone morphogenetic proteins. Background information about this topic, including panel materials... appropriate organizations with expertise in the use of bone morphogenetic protein. II. Meeting Format This...

An ultrastructural and immunogold localization study of proteoglycans associated with the osteocytes of fetal bone in osteogenesis imperfecta.

PubMed

Sarathchandra, P; Pope, F M; Ali, S Y

1996-06-01

Osteogenesis imperfecta (OI) is a rare, heterogeneous, inherited connective tissue disorder frequently caused by abnormalities of type I collagen. It is characterized by bone fragility, osteopenia, and progressive skeletal deformities. Electron microscopy of three OI type II fetal bone samples revealed numerous large osteocyte lacunae. In addition, there was a perilacunar osteoid-like band of collagen surrounding the osteocytes, which was unmineralized and morphologically unusual. Furthermore, large osteocyte lacunae contained fine particles and filamentous material similar to the expected ultrastructural appearance of proteoglycans. More detailed examination was carried out using histochemical and immunogold localization of proteoglycans at light and ultrastructural levels. These tests and the use of electron probe X-ray microanalysis confirmed that the material in the osteocyte lacunae was proteoglycan. In contrast, in the age- and site-matched normal fetal bone, all the osteocyte lacunae appeared negative for proteoglycan. Proteoglycans are regarded as inhibitors of calcification. Our observation of substantial amounts of proteoglycan in abnormally enlarged osteocytic lacunae of some OI fetal bone suggests association with the abnormal bone of this particular subtype of OI type II.

The Influence of Primary Microenvironment on Prostate Cancer Osteoblastic Bone Lesion Development

DTIC Science & Technology

2015-09-01

for inhibiting PCa bone lesion development: 3a. Basic fibroblast growth factor (bFGF) in PC3 bone metastasis: bFGF was identified by cytokine...II receptor (TβRII) knockout (Tgfbr2 KO) mouse models. Col1creERT/Tgfbr2 KO (Col/Tgfbr2 KO), which have TGF-β signaling specific KO in fibroblasts ... fibroblasts and osteoblasts in the bone by Colcre/Tgfbr2 KO, or in the myeloid lineage cells, including osteoclasts in the bone by LysMcre/Tgfbr2 KO

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

PubMed

Bateman, Marjorie E; Strong, Amy L; Hunter, Ryan S; Bratton, Melyssa R; Komati, Rajesh; Sridhar, Jayalakshmi; Riley, Kevin E; Wang, Guangdi; Hayes, Daniel J; Boue, Stephen M; Burow, Matthew E; Bunnell, Bruce A

2017-04-15

While current therapies for osteoporosis focus on reducing bone resorption, the development of therapies to regenerate bone may also be beneficial. Promising anabolic therapy candidates include phytoestrogens, such as daidzein, which effectively induce osteogenesis of adipose-derived stromal cells (ASCs) and bone marrow stromal cells (BMSCs). To investigate the effects of glyceollins, structural derivatives of daidzein, on osteogenesis of ASCs and BMSCs. Herein, the osteoinductive effects of glyceollin I and glyceollin II were assessed and compared to estradiol in ASCs and BMSCs. The mechanism by which glyceollin II induces osteogenesis was further examined. The ability of glyceollins to promote osteogenesis of ASCs and BMSCs was evaluated in adherent and scaffold cultures. Relative deposition of calcium was analyzed using Alizarin Red staining, Bichinchoninic acid Protein Assay, and Alamar Blue Assay. To further explore the mechanism by which glyceollin II exerts its osteoinductive effects, docking studies of glyceollin II, RNA isolation, cDNA synthesis, and quantitative RT-PCR (qPCR) were performed. In adherent cultures, ASCs and BMSCs treated with estradiol, glyceollin I, or glyceollin II demonstrated increased calcium deposition relative to vehicle-treated cells. During evaluation on PLGA scaffolds seeded with ASCs and BMSCs, glyceollin II was the most efficacious in inducing ASC and BMSC osteogenesis compared to estradiol and glyceollin I. Dose-response analysis in ASCs and BMSCs revealed that glyceollin II has the highest potency at 10nM in adherent cultures and 1µM in tissue scaffold cultures. At all doses, osteoinductive effects were attenuated by fulvestrant, suggesting that glyceollin II acts at least in part through estrogen receptor-mediated pathways to induce osteogenesis. Analysis of gene expression demonstrated that, similar to estradiol, glyceollin II induces upregulation of genes involved in osteogenic differentiation. The ability of glyceollin II to induce osteogenic differentiation in ASCs and BMSCs indicates that glyceollins hold the potential for the development of pharmacological interventions to improve clinical outcomes of patients with osteoporosis. Copyright © 2017 Elsevier GmbH. All rights reserved.

Orthopedic devices; classification for the resorbable calcium salt bone void filler device. Final rule.

PubMed

2003-06-02

The Food and Drug Administration (FDA) is classifying the resorbable calcium salt bone void filler device intended to fill bony voids or gaps of the extremities, spine, and pelvis that are caused by trauma or surgery and are not intrinsic to the stability of the bony structure into class II (special controls). Elsewhere in this issue of the Federal Register, FDA is announcing the availability of a class II special controls guidance entitled "Class II Special Controls Guidance Document: Resorbable Calcium Salt Bone Void Filler Device; Guidance for Industry and FDA." This action is being undertaken based on new information submitted in a classification proposal from Wright Medical Technology under the Federal Food, Drug, and Cosmetic Act as amended by the Medical Device Amendments of 1976, the Safe Medical Devices Act of 1990, and the Food and Drug Administration Modernization Act of 1997.

Depressive symptoms are not associated with forearm bone accrual during adolescence.

PubMed

Lourenço, Sara; Lucas, Raquel; da Silva, Daniele Ferreira; Ramos, Elisabete; Barros, Henrique

2014-01-01

Although depression has been associated to worst bone physical properties in adulthood, this study showed that depressive symptoms were not significantly associated to bone mineral density measured at the forearm during adolescence. Depressive conditions have been related to the reduction of bone mineral density (BMD) in adulthood. Though it is possible to hypothesize that depressive symptoms present similar effects in bone mineral accrual during adolescence, such association is poorly researched. Therefore, we aimed to study the relation between depressive symptoms and forearm BMD during adolescence. The study is based on the Epidemiological Health Investigation of Teenagers cohort that sampled adolescents born in 1990 and enrolled in public and private schools of Porto during the 2003/2004 academic year. At baseline (n = 2,160) and at 17 years of age (n = 1,716), depressive symptoms were evaluated using the Beck Depression Inventory-II (BDI-II). BMD (grams per square centimetre) was measured at the non-dominant forearm using dual-energy X-ray absorptiometry. Sex-specific crude and adjusted linear regression coefficients (β) and the corresponding 95 % confidence intervals (95 % CIs) were calculated to estimate the cross-sectional and prospective associations between depressive symptoms and forearm BMD. In both sexes, in early and late adolescence, depressive symptoms presented no statistically significant association with forearm BMD (β Girls13 = 0.09, 95 % CI = -0.43 to 0.61; β Girls17 = 0.10, 95 % CI = -0.43 to 0.64; β Boys13 = -0.10, 95 % CI = -0.96 to 0.76; β Boys17 = 0.49, 95 % CI = -0.96 to 1.93). Similarly, there were no significant associations between depressive symptoms and the annual forearm BMD change during adolescence in girls and boys (β Girls_BDI-II_13-17_remained_lowest = -0.85, 95 % CI = -4.62 to 2.92 vs. β Girls_BDI-II_13-17_remained_highest = -1.87, 95 % CI = -5.06 to 1.31; β Boys_BDI-II_13-17_remained_lowest = 0.48, 95 % CI = -5.30 to 6.26 vs. β Boys_BDI-II_13-17_remained_highest = 1.36, 95 % CI = -3.25 to 5.97). Depressive symptoms, with the range of severity observed in the general adolescent population, were not associated with changes in forearm bone mineral density during adolescence. Further research based on measurements of different skeletal sites is needed in order to detect a systemic effect of depression on growing bone.

Intra-oral soft tissue expansion and volume stability of onlay bone grafts.

PubMed

Abrahamsson, Peter

2011-01-01

Insufficient regeneration of missing bone and soft-tissue may present aesthetic or functional problems in patients indicated for dental implant surgery. Several techniques such as bone grafts, bone substitutes and guided tissue regeneration (GTR) have been described to rebuild a compromised alveolar ridge. Adequate soft-tissue coverage of grafted bone and titanium-mesh is important to avoid exposure which may result in loss of the bone graft. The general aim of this thesis was to evaluate use of an osmotic tissue expander for expanding intra-oral soft tissue--creating a surplus of soft tissue-- in preparation for onlay bone grafting. An experimental rabbit model was used in studies (I), (II) and (III). In (I) an osmotic soft-tissue expander was placed bilaterally on the lateral wall of the mandible via an extra-oral approach. After two weeks of expansion the rabbits were killed and specimens were collected for histology. No inflammatory reaction and no resorbtion of the cortical bone occured. The periosteum was expanded and new bone formation was seen in the edges of the expander. In (II) and (III) the expander was placed under the periosteum in the same way as in (I): bilaterally in 13 rabbits in (II) and unilaterally in 11 rabbits in (III). After two weeks of expansion the expander was identified and removed. In (II) particulated bone was placed at the recipient site protected by a titanium mesh in one site and a bio-resorbable mesh on the other site. In (III), DBBM particles and bone particles collected from the lateral border of the mandible separated by a collagen membrane was placed at the recipient site. The graft was protected by a pre-bent titanium mesh covered by a collagen membrane. After a healing period of 3 months specimens were collected for histological and SEM examination. New bone was growing in direct contact with the titanium mesh and bio resorbable mesh. The newly formed bone had the same calcium content as the mature bone in the base of the mandible. In the clinical study (IV) 20 patients were consecutively recruited and randomised into two groups. The experimental group (ten patients) had an osmotic soft tissue expander implanted. After two weeks of expansion the expander was removed and a particulated bone graft protected by a titanium mesh and a collagen membrane was fixed to the recipient site. Titanium implants were installed after a healing period of 6 months. The patients in the reference group had a bone block grafted from the anterior ramus fixated to the recipient site with one or two titanium mini screws. Implants were installed after a healing period of 6 months. A three dimensional optical measuring device was used to measure alterations in the soft tissue profile before each surgical procedure. The three-dimensional changes were then analysed on a PC. The results from the clinical study in patients confirmed the results from the experimental rabbit studies. The osmotic tissue expander expanded the soft tissue. Expander perforations of the soft tissue occurred in two patients. The optical measurements demonstrated a positive volume gain after soft tissue expansion and bone grafting. The expanded tissue could be used to cover a bone graft. There still was a risk of mesh exposure, even after soft tissue expansion, which occurred in two patients. In both groups, implants could be installed in the grafted bone in positions that would allow the crowns to fit aesthetically into the dental arch.

Cortical bone stress distribution in mandibles with different configurations restored with prefabricated bar-prosthesis protocol: a three-dimensional finite-element analysis.

PubMed

de Almeida, Erika Oliveira; Rocha, Eduardo Passos; Assunção, Wirley Gonçalves; Júnior, Amílcar Chagas Freitas; Anchieta, Rodolfo Bruniera

2011-01-01

To evaluate stress distribution in different horizontal mandibular arch formats restored by protocol-type prostheses using three-dimensional finite element analysis (3D-FEA). A representative model (M) of a completely edentulous mandible restored with a prefabricated bar using four interforaminal implants was created using SolidWorks 2010 software (Inovart, São Paulo, Brazil) and analyzed by Ansys Workbench 10.0 (Swanson Analysis Inc., Houston, PA) to obtain the stress fields. Three mandibular arch sizes were considered for analysis, regular (M), small (MS), and large (ML). Three unilateral posterior loads (L) (150 N) were used: perpendicular to the prefabricated bar (L1); 30° oblique in a buccolingual direction (L2); 30° oblique in a lingual-buccal direction (L3). The maximum and minimum principal stresses (σ(max), σ(min)), the equivalent von Mises (σ(vM)), and the maximum principal strain (σ(max) ) were obtained for type I (M.I) and type II (M.II) cortical bones. Tensile stress was more evident than compression stress in type I and II bone; however, type II bone showed lower stress values. The L2 condition showed highest values for all parameters (σ(vM), σ(max), σ(min), ɛ(max)). The σ(vM) was highest for the large and small mandibular arches. The large arch model had a higher influence on σ(max) values than did the other formats, mainly for type I bone. Vertical and buccolingual loads showed considerable influence on both σ(max) and σ(min) stresses. © 2010 by The American College of Prosthodontists.

An individualised risk-adapted protocol of pre- and post transplant zoledronic acid reduces bone loss after allogeneic stem cell transplantation: results of a phase II prospective trial.

PubMed

Grigg, A; Butcher, B; Khodr, B; Bajel, A; Hertzberg, M; Patil, S; D'Souza, A B; Ganly, P; Ebeling, P; Wong, E

2017-09-01

Bone loss occurs frequently following allogeneic haematopoietic stem cell transplantation (alloSCT). The Australasian Leukaemia and Lymphoma Group conducted a prospective phase II study of pretransplant zoledronic acid (ZA) and individualised post-transplant ZA to prevent bone loss in alloSCT recipients. Patients received ZA 4 mg before conditioning. Administration of post-transplant ZA from days 100 to 365 post alloSCT was determined by a risk-adapted algorithm based on serial bone density assessments and glucocorticoid exposure. Of 82 patients enrolled, 70 were alive and without relapse at day 100. A single pretransplant dose of ZA prevented femoral neck bone loss at day 100 compared with baseline (mean change -2.6±4.6%). Using the risk-adapted protocol, 42 patients received ZA between days 100 and 365 post alloSCT, and this minimised bone loss at day 365 compared with pretransplant levels (mean change -2.9±5.3%). Femoral neck bone loss was significantly reduced in ZA-treated patients compared with historical untreated controls at days 100 and 365. This study demonstrates that a single dose of ZA pre-alloSCT prevents femoral neck bone loss at day 100 post alloSCT, and that a risk-adapted algorithm is able to guide ZA administration from days 100 to 365 post transplant and minimise further bone loss.

Clinical features and radiological evaluation of otic capsule sparing temporal bone fractures.

PubMed

Song, S W; Jun, B C; Kim, H

2017-03-01

To evaluate the clinical and radiological aspects of otic capsule sparing temporal bone fractures. Using medical records, 188 temporal bones of 173 patients with otic capsule sparing temporal bone fractures were evaluated. Otoscopic findings and symptoms, facial paralysis, and hearing loss were assessed. Using regional analysis, 7 fractures were classified as type I, 85 as type II, 169 as type III and 114 as type IV. Fourteen of the 17 facial paralysis cases improved to House-Brackmann grade II or lower at an average of 57.6 days after the initial evaluation. Thirty-one patients underwent initial and follow-up pure tone audiometry examinations. The air-bone gap closed significantly from 27.2 dB at an average of 21.8 days post-trauma to 19.6 dB at an average of 79.9 days post-trauma, without the need for surgical intervention. Initial conservative treatment for facial paralysis or conductive hearing loss is possible in otic capsule sparing fracture cases after careful evaluation of the patient.

[Toxic phosphorous osteonecrosis of facial bones among drug addicts to desomorphine and pervitin. Part II].

PubMed

Basin, E M; Medvedev, Yu A

2015-01-01

Article describes literature review of "atypical" osteomyelitis--osteonecrosis of facial bones among addicts to synthetic narcotics desomorphine and pervitin, different comorbidities, treatment strategy and prognosis were outlined

Suture anchor fixation strength with or without augmentation in osteopenic and severely osteoporotic bones in rotator cuff repair: a biomechanical study on polyurethane foam model.

PubMed

Er, Mehmet Serhan; Altinel, Levent; Eroglu, Mehmet; Verim, Ozgur; Demir, Teyfik; Atmaca, Halil

2014-08-22

The purpose of the present study was to compare the results of various types of anchor applications with or without augmentation in both osteopenic and severely osteoporotic bone models. Two different types of suture anchors were tested in severely osteoporotic (SOP) and osteopenic polyurethane (PU) foam blocks using an established protocol. An Instron machine applied static loading parallel to the axis of insertion until failure, and the mean anchor failure strengths were calculated. The mode of failure (anchor pullout, suture tear) was recorded. The anchors tested included the Corkscrew (CS) (Arthrex Inc., Naples, FL, USA) (without augmentation, polymethylmethacrylate (PMMA)-augmented, and bioabsorbable tricalcium phosphate (TCP) cement-augmented) and Corkscrew FT II (CS FT II) 5.5 mm (without augmentation as used routinely). The mean failure loads for both SOP and osteopenic PU foam blocks, respectively, were as follows: CS, 16.2 and 212.4 N; CS with TCP, 75.2 and 396 N; CS with PMMA, 101.2 and 528.8 N; CS FT II, 13.8 and 339.8 N. Augmentation of CS with TCP or PMMA would be essential to SOP bones. In the osteopenic bone model, although anchor fixation augmented with PMMA is the best fixation method, CS augmented with TCP cement or CS FT II without any need for augmentation may also be used as an alternative.

PERFORMANCE OF CONVENTIONAL PCRs BASED ON PRIMERS DIRECTED TO NUCLEAR AND MITOCHONDRIAL GENES FOR THE DETECTION AND IDENTIFICATION OF Leishmania spp.

PubMed Central

LOPES, Estela Gallucci; GERALDO, Carlos Alberto; MARCILI, Arlei; SILVA, Ricardo Duarte; KEID, Lara Borges; OLIVEIRA, Trícia Maria Ferreira da Silva; SOARES, Rodrigo Martins

2016-01-01

In visceral leishmaniasis, the detection of the agent is of paramount importance to identify reservoirs of infection. Here, we evaluated the diagnostic attributes of PCRs based on primers directed to cytochrome-B (cytB), cytochrome-oxidase-subunit II (coxII), cytochrome-C (cytC), and the minicircle-kDNA. Although PCRs directed to cytB, coxII, cytC were able to detect different species of Leishmania, and the nucleotide sequence of their amplicons allowed the unequivocal differentiation of species, the analytical and diagnostic sensitivity of these PCRs were much lower than the analytical and diagnostic sensitivity of the kDNA-PCR. Among the 73 seropositive animals, the asymptomatic dogs had spleen and bone marrow samples collected and tested; only two animals were positive by PCRs based on cytB, coxII, and cytC, whereas 18 were positive by the kDNA-PCR. Considering the kDNA-PCR results, six dogs had positive spleen and bone marrow samples, eight dogs had positive bone marrow results but negative results in spleen samples and, in four dogs, the reverse situation occurred. We concluded that PCRs based on cytB, coxII, and cytC can be useful tools to identify Leishmania species when used in combination with automated sequencing. The discordance between the results of the kDNA-PCR in bone marrow and spleen samples may indicate that conventional PCR lacks sensitivity for the detection of infected dogs. Thus, primers based on the kDNA should be preferred for the screening of infected dogs. PMID:27253743

Evaluation of lipid peroxidation and antioxidant defense mechanisms in the bone of rats in conditions of separate and combined administration of vanadium (V) and magnesium (Mg).

PubMed

Ścibior, Agnieszka; Gołębiowska, Dorota; Adamczyk, Agnieszka; Kurus, Joanna; Staniszewska, Magdalena; Sadok, Ilona

2018-03-25

The impact of vanadium (V) and magnesium (Mg) applied as sodium metavanadate (SMV, 0.125 mg V/ml) and magnesium sulfate (MS, 0.06 mg Mg/ml) on oxidative stress markers in bone of male Wistar rats was investigated. Some of them were also measured in the liver, e.g. l-ascorbic acid (hepatic L-AA). Additionally, relationships between selected indices determined in bone were examined. SMV alone (Group II) did not significantly alter the level of TBARS and the activity of SOD, compared with the control (Group I), but it slightly reduced the GR activity (by 13%) and the L-AA level (by 15.5%). It also markedly lowered the activity of CAT and GPx (by 34% and 29%), and to some degree elevated the activity of GST (by 16%) and the hepatic L-AA level (by 119%). MS alone (Group III) decreased the TBARS level (by 49%), slightly lowered the L-AA concentration (by 14%), and reduced the SOD, GPx, and GR activities (by 31%, 40%, and 28%), but did not change the activity of CAT, compared with the control. Additionally, it elevated the GST activity (by 56%) and the hepatic L-AA level (by 40%). In turn, the SMV + MS combination (Group IV) reduced the TBARS level (by 38%) and the SOD, CAT, GPx, and GR activities (by 61%, 58%, 72%, and 40%) but elevated the GST activity (by 66%), compared with the control. The activity of SOD and GPx in the rats in Group IV was also reduced, compared with Group II (by 61% and 61%) and Group III (by 44% and 54%). In turn, the activities of CAT and GR were decreased, compared with Group III (by 55%) and Group II (by 31%), and the L-AA level was lowered, in comparison with Groups II and III (by 53% and 54%). Further, the concentration of V in the bone of rats in Groups II and IV increased, whereas the concentration of Mg decreased, compared with Groups I and III, in which the V and Mg levels dropped and were not altered, respectively, compared with Group I. The total content of Fe in the bone of rats in Groups II and IV increased, compared with Group III, in which the total Fe content did not change, compared with Group I. In turn, the total bone Cu content significantly decreased in the rats in Groups III and IV, compared with Groups I and II, whereas the total Zn content and the Ca concentration did not change markedly. The results provided evidence that the concentration of V used as SMV did not enhance LPO in bone, whereas Mg, at the selected level, markedly reduced LPO in this tissue. On the other hand, both elements administered separately and in combination disrupted the antioxidant defense mechanisms and homeostasis of some metals in bone tissue, which consequently may have contributed to disturbances in the balance in the activities of osteoblastic and osteoclastic cells, and thereby negatively affected bone health. Copyright © 2018 Elsevier B.V. All rights reserved.

Expression of the genes for insulin-like growth factors and their receptors in bone during skeletal growth

NASA Technical Reports Server (NTRS)

Bikle, D. D.; Harris, J.; Halloran, B. P.; Roberts, C. T.; Leroith, D.; Morey-Holton, E.

1994-01-01

Insulin-like growth factors (IGF) are important regulators of skeletal growth. To determine whether the capacity to produce and respond to these growth factors changes during skeletal development, we measured the protein and mRNA levels for IGF-I, IGF-II, and their receptors (IGF-IR and IGF-IIR, respectively) in the tibia and femur of rats before and up to 28 mo after birth. The mRNA levels remained high during fetal development but fell after birth, reaching a nadir by 3-6 wk. This fall was most pronounced for IGF-II and IGF-IIR mRNA and least pronounced for IGF-I mRNA. However, after 6 wk, both IGF-I and IGF-IR mRNA levels recovered toward the levels observed at birth. In the prenatal bones, the signals for the mRNAs of IGF-II and IGF-IIR were stronger than the signals for the mRNAs of IGF-I and IGF-IR, although the content of IGF-I was three- to fivefold greater than that of IGF-II. IGF-II levels fell postnatally, whereas the IGF-I content rose after birth such that the ratio IGF-I/IGF-II continued to increase with age. We conclude that, during development, rat bone changes its capacity to produce and respond to IGFs with a progressive trend toward the dominance of IGF-I.

Cartilage Protective and Chondrogenic Capacity of WIN-34B, a New Herbal Agent, in the Collagenase-Induced Osteoarthritis Rabbit Model and in Progenitor Cells from Subchondral Bone

PubMed Central

Huh, Jeong-Eun; Park, Yeon-Cheol; Seo, Byung-Kwan; Lee, Jae-Dong; Baek, Yong-Hyeon; Choi, Do-Young; Park, Dong-Suk

2013-01-01

We sought to determine the cartilage repair capacity of WIN-34B in the collagenase-induced osteoarthritis rabbit model and in progenitor cells from subchondral bone. The cartilage protective effect of WIN-34B was measured by clinical and histological scores, cartilage area, and proteoglycan and collagen contents in the collagenase-induced osteoarthritis rabbit model. The efficacy of chondrogenic differentiation of WIN-34B was assessed by expression of CD105, CD73, type II collagen, and aggrecan in vivo and was analyzed by the surface markers of progenitor cells, the mRNA levels of chondrogenic marker genes, and the level of proteoglycan, GAG, and type II collagen in vitro. Oral administration of WIN-34B significantly increased cartilage area, and this was associated with the recovery of proteoglycan and collagen content. Moreover, WIN-34B at 200 mg/kg significantly increased the expression of CD105, CD73, type II collagen, and aggrecan compared to the vehicle group. WIN-34B markedly enhanced the chondrogenic differentiation of CD105 and type II collagen in the progenitor cells from subchondral bone. Also, we confirmed that treatment with WIN-34B strongly increased the number of SH-2(CD105) cells and expression type II collagen in subchondral progenitor cells. Moreover, WIN-34B significantly increased proteoglycan, as measured by alcian blue staining; the mRNA level of type II α1 collagen, cartilage link protein, and aggrecan; and the inhibition of cartilage matrix molecules, such as GAG and type II collagen, in IL-1β-treated progenitor cells. These findings suggest that WIN-34B could be a potential candidate for effective anti-osteoarthritic therapy with cartilage repair as well as cartilage protection via enhancement of chondrogenic differentiation in the collagenase-induced osteoarthritis rabbit model and progenitor cells from subchondral bone. PMID:23983790

21 CFR 874.3300 - Hearing Aid.

Code of Federal Regulations, 2010 CFR

2010-04-01

... generic type of device includes the air-conduction hearing aid and the bone-conduction hearing aid, but... subpart E of part 807 of this chapter subject to § 874.9. (2) Class II for the bone-conduction hearing aid...

21 CFR 874.3300 - Hearing Aid.

Code of Federal Regulations, 2012 CFR

2012-04-01

... generic type of device includes the air-conduction hearing aid and the bone-conduction hearing aid, but... subpart E of part 807 of this chapter subject to § 874.9. (2) Class II for the bone-conduction hearing aid...

21 CFR 874.3300 - Hearing Aid.

Code of Federal Regulations, 2014 CFR

2014-04-01

... generic type of device includes the air-conduction hearing aid and the bone-conduction hearing aid, but... subpart E of part 807 of this chapter subject to § 874.9. (2) Class II for the bone-conduction hearing aid...

21 CFR 874.3300 - Hearing Aid.

Code of Federal Regulations, 2013 CFR

2013-04-01

... generic type of device includes the air-conduction hearing aid and the bone-conduction hearing aid, but... subpart E of part 807 of this chapter subject to § 874.9. (2) Class II for the bone-conduction hearing aid...

21 CFR 874.3300 - Hearing Aid.

Code of Federal Regulations, 2011 CFR

2011-04-01

... generic type of device includes the air-conduction hearing aid and the bone-conduction hearing aid, but... subpart E of part 807 of this chapter subject to § 874.9. (2) Class II for the bone-conduction hearing aid...

Engraftment Efficiency after Intra-Bone Marrow versus Intravenous Transplantation of Bone Marrow Cells in a Canine Nonmyeloablative Dog Leukocyte Antigen-Identical Transplantation Model.

PubMed

Lange, Sandra; Steder, Anne; Killian, Doreen; Knuebel, Gudrun; Sekora, Anett; Vogel, Heike; Lindner, Iris; Dunkelmann, Simone; Prall, Friedrich; Murua Escobar, Hugo; Freund, Mathias; Junghanss, Christian

2017-02-01

An intra-bone marrow (IBM) hematopoietic stem cell transplantation (HSCT) is assumed to optimize the homing process and therefore to improve engraftment as well as hematopoietic recovery compared with conventional i.v. HSCT. This study investigated the feasibility and efficacy of IBM HSCT after nonmyeloablative conditioning in an allogeneic canine HSCT model. Two study cohorts received IBM HSCT of either density gradient (IBM-I, n = 7) or buffy coat (IBM-II, n = 6) enriched bone marrow cells. An historical i.v. HSCT cohort served as control. Before allogeneic HSCT experiments were performed, we investigated the feasibility of IBM HSCT by using technetium-99m marked autologous grafts. Scintigraphic analyses confirmed that most IBM-injected autologous cells remained at the injection sites, independent of the applied volume. In addition, cell migration to other bones occurred. The enrichment process led to different allogeneic graft volumes (IBM-I, 2 × 5 mL; IBM-II, 2 × 25 mL) and significantly lower counts of total nucleated cells in IBM-I grafts compared with IBM-II grafts (1.6 × 10 8 /kg versus 3.8 × 10 8 /kg). After allogeneic HSCT, dogs of the IBM-I group showed a delayed engraftment with lower levels of donor chimerism when compared with IBM-II or to i.v. HSCT. Dogs of the IBM-II group tended to reveal slightly faster early leukocyte engraftment kinetics than intravenously transplanted animals. However, thrombocytopenia was significantly prolonged in both IBM groups when compared with i.v. HSCT. In conclusion, IBM HSCT is feasible in a nonmyeloablative HSCT setting but failed to significantly improve engraftment kinetics and hematopoietic recovery in comparison with conventional i.v. HSCT. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Prokaryotic expression of bone sialoprotein and identification of casein kinase II phosphorylation sites.

PubMed

Saad, Fawzy A; Salih, Erdjan; Wunderlich, Livius; Flückiger, Rudolf; Glimcher, Melvin J

2005-07-29

Bone sialoprotein is an extracellular noncollagenous acidic protein that plays a role in bone mineralization and remodeling. Its expression is restricted to mineralized tissues and is subjected to variety of posttranslational modifications including phosphorylation and glycosylation. We have expressed the full-length and half domains of bovine bone sialoprotein in a prokaryotic system and identified the phosphorylation sites of casein kinase II. The N-terminal automated solid-phase sequencing defined four phosphorylated peptides: residues 28-38 (LEDS(P)EENGVFK), 51-86 (FYPELKRFAVQSSS(P)DS(P)S(P)EENGNGDS(P)S(P)EEEEEEEETS(P)), 151-165 (EDES(P)DEEEEEEEEEE), and 295-305 (GRGYDS(P)YDGQD). Nine phosphoserines were identified within the four peptides. Seven of them were in the N-terminus (S31, S64, S66, S67, S75, S76, and S86) and two were in the C-terminus (S154 and S300) of the protein.

Unraveling hominin behavior at another anthropogenic site from Olduvai Gorge (Tanzania): new archaeological and taphonomic research at BK, Upper Bed II.

PubMed

Domínguez-Rodrigo, M; Mabulla, A; Bunn, H T; Barba, R; Diez-Martín, F; Egeland, C P; Espílez, E; Egeland, A; Yravedra, J; Sánchez, P

2009-09-01

New archaeological excavations and research at BK, Upper Bed II (Olduvai Gorge, Tanzania) have yielded a rich and unbiased collection of fossil bones. These new excavations show that BK is a stratified deposit formed in a riverine setting close to an alluvial plain. The present taphonomic study reveals the second-largest collection of hominin-modified bones from Olduvai, with abundant cut marks found on most of the anatomical areas preserved. Meat and marrow exploitation is reconstructed using the taphonomic signatures left on the bones by hominins. Highly cut-marked long limb shafts, especially those of upper limb bones, suggest that hominins at BK were actively engaged in acquiring small and middle-sized animals using strategies other than passive scavenging. The exploitation of large-sized game (Pelorovis) by Lower Pleistocene hominins, as suggested by previous researchers, is supported by the present study.

Contour changes in human alveolar bone following tooth extraction of the maxillary central incisor.

PubMed

Li, Bei; Wang, Yao

2014-12-01

The purpose of this study was to apply cone-beam computed tomography (CBCT) to observe contour changes in human alveolar bone after tooth extraction of the maxillary central incisor and to provide original morphological evidence for aesthetic implant treatment in the maxillary anterior area. Forty patients were recruited into the study. Each patient had two CBCT scans (CBCT I and CBCT II), one taken before and one taken three months after tooth extraction of maxillary central incisor (test tooth T). A fixed anatomic reference point was used to orient the starting axial slice of the two scans. On three CBCT I axial slices, which represented the deep, middle, and shallow layers of the socket, labial and palatal alveolar bone widths of T were measured. The number of sagittal slices from the start point to the pulp centre of T was recorded. On three CBCT II axial slices, the pulp centres of extracted T were oriented according to the number of moved sagittal slices recorded in CBCT I. Labial and palatal alveolar bone widths at the oriented sites were measured. On the CBCT I axial slice which represented the middle layer of the socket, sagittal slices were reconstructed. Relevant distances of T on the sagittal slice were measured, as were the alveolar bone width and tooth length of the opposite central incisor. On the CBCT II axial slice, which represented the middle layer of the socket, relevant distances recorded in CBCT I were transferred on the sagittal slice. The height reduction of alveolar bone on labial and palatal sides was measured, as were the alveolar bone width and tooth length of the opposite central incisor at the oriented site. Intraobserver reliability assessed by intraclass correlation coefficients (ICCs) was high. Paired sample t-tests were performed. The alveolar bone width and tooth length of the opposite central incisor showed no statistical differences (P<0.05). The labial alveolar bone widths of T at the deep, middle, and shallow layers all showed statistical differences. However, no palatal alveolar bone widths showed any statistical differences. The width reduction of alveolar bone was 1.2, 1.6, and 2.7 mm at the deep, middle, and shallow layers, respectively. The height reduction of alveolar bone on labial and palatal sides of T both showed statistical differences, which was 1.9 and 1.1 mm, respectively.

Angiotensin (1-7) ameliorates the structural and biochemical alterations of ovariectomy-induced osteoporosis in rats via activation of ACE-2/Mas receptor axis.

PubMed

Abuohashish, Hatem M; Ahmed, Mohammed M; Sabry, Dina; Khattab, Mahmoud M; Al-Rejaie, Salim S

2017-05-23

The local and systemic renin angiotensin system (RAS) influences the skeletal system micro-structure and metabolism. Studies suggested angiotensin 1-7 (Ang(1-7)) as the beneficial RAS molecule via Mas receptor activation. This study examines the function of Ang(1-7) in bone micro-architecture and metabolism in an ovariectomized (OVX) rodent model of osteoporosis. OVX rats showed structural and bone metabolic degeneration in parallel with suppressed expressions of the angiotensin converting enzyme-2 (ACE-2)/Ang(1-7)/Mas components. The infusion of Ang(1-7) markedly alleviated the altered bone metabolism and significantly enhanced both trabecular (metaphyseal) and cortical (metaphyseal-diaphyseal) morphometry. Urinary and bones minerals were also improved in OVX rats by Ang(1-7). The infusion of the heptapeptide enhanced ACE-2/Mas receptor expressions, while down-regulated AngII, ACE, and AngII type-1 receptor (AT1R) in OVX animals. Moreover, Ang(1-7) markedly improved osteoprotegerin (OPG) and lowered receptor activator NF-κB ligand (RANKL) expressions. The defensive properties of Ang(1-7) on bone metabolism, structure and minerals were considerably eradicated after blockage of Mas receptor with A-779. Ang(1-7)-induced up-regulated ACE-2/Ang(1-7)/Mas cascade and OPG expressions were abolished and the expressions of ACE/AngII/AT1R and RANKL were provoked by A-779. These findings shows for the first time the novel valuable therapeutic role of Ang(1-7) on bone health and metabolism through the ACE-2/Mas cascade.

Bone Sialoproteins and Breast Cancer Detection

DTIC Science & Technology

2004-07-01

used to follow proteolytic activity on more natural macromolecular substrates. These substrates are so highly substituted with fluorescein moieties that...uninformative for breast cancer, but does correlate with bone mineral density, parathyroid hormone and phosphorus . (Summary of Appendix II). Normal MEPE...calcium, phosphorus , vitamin D, as well as novel phosphatonin(s), and the bone and kidney organs. Candidate phosphaturic factors include MEPE; PHEX, a

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

PubMed

Sklaroff, R B; Sklaroff, D M

1976-07-01

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

In vitro stabilization of a low-tin bone-imaging agent (99mTc-Sn-HEDP) by ascorbic acid.

PubMed

Tofe, A J; Francis, M D

1976-09-01

The presence of oxidants in the 99mTc-pertechnetate and of oxygen in diagnostic kits containing low concentrations of Sn(II) has a detrimental effect upon in vitro and in vivo stability. Maintaining a nitrogen atmosphere or increasing the Sn(II) concentration inhibits the formation of 99mTcO4-. However, the latter remedy is likely to cause uptake in the reticuloendothelial system and has been associated with false positive or negative brain scans. We used ascorbic acid (an antioxidant) to ensure the in vitro stability with the low-Sn(II) bone agent disodium etidronate. In vitro stability studies by instant thin-layer chromatography, using high-acitivity generators and "instant pertechnetate," yielded less than 2% free pertechnetate at 24 hr after preparation. Distribution studies in guinea pigs show neither altered distribution of the bone agent nor abnormal distribution of ascorbic acid, suggesting its sole function as a noncomplexing stabilizer.

Strain gauges used in the mechanical testing of bones. Part II: "In vitro" and "in vivo" technique.

PubMed

Cordey, J; Gautier, E

1999-01-01

How to choose and prepare the strain gauges for bonding on bones "in vitro" and "in vivo"? This communication aims to elucidate technical details and some applications: direct assessment of the axial load, the bending moment, and the torque applied to long bones by the physiological loads. As a typical example of application, we will show the assessment of stress protection due to plates on the bones in the sheep tibia.

Effects of laser photherapy on bone defects grafted with mineral trioxide aggregate, bone morphogenetic proteins, and guided bone regeneration: a Raman spectroscopic study.

PubMed

Pinheiro, Antonio L B; Aciole, Gilberth T S; Cangussú, Maria Cristina T; Pacheco, Marcos T T; Silveira, Landulfo

2010-12-15

We have used Raman analysis to assess bone healing on different models. Benefits on the isolated or combined use of mineral trioxide aggregate, bone morphogenetic proteins, guided bone regeneration and laser on bone repair have been reported, but not their combination. We studied peaks of hydroxyapatite and CH groups on defects grafted with MTA, treated or not with laser, BMPs, and GBR. Ninety rats were divided in 10 groups each, subdivided into three subgroups. Laser (λ850 nm) was applied at every other day for 2 weeks. Raman readings were taken at the surface of the defect. Statistical analysis (CHA) showed significant differences between all groups (p = 0.001) and between Group II and all other (p < 0.001), but not with Group X (p = 0.09). At day 21 differences were seen between all groups (p = 0.031) and between Groups VIII and X when compared with Groups VI (p = 0.03), V (p < 0.001), IV (p < 0.001), and IX (p = 0.04). At the end of the experimental period no significant differences were seen. On regards CH, significant differences were seen at the 15(th) day (p = 0.002) and between Group II and all other groups (p < 0.0001) but not with control. Advanced maturation on irradiated bone is because of increased secretion of calcium hydroxyapatite (CHA) that is indicative of greater calcification and resistance of the bone. We conclude that the association of the MTA with laser phototherapy (LPT) and/or not with GBR resulted in a better bone repair. The use of the MTA associated to IR LPT resulted in a more advanced and quality bone repair. Copyright © 2010 Wiley Periodicals, Inc.

Characterization and evaluation of graphene oxide scaffold for periodontal wound healing of class II furcation defects in dog.

PubMed

Kawamoto, Kohei; Miyaji, Hirofumi; Nishida, Erika; Miyata, Saori; Kato, Akihito; Tateyama, Akito; Furihata, Tomokazu; Shitomi, Kanako; Iwanaga, Toshihiko; Sugaya, Tsutomu

2018-01-01

The 3-dimensional scaffold plays a key role in volume and quality of repair tissue in periodontal tissue engineering therapy. We fabricated a novel 3D collagen scaffold containing carbon-based 2-dimensional layered material, named graphene oxide (GO). The aim of this study was to characterize and assess GO scaffold for periodontal tissue healing of class II furcation defects in dog. GO scaffolds were prepared by coating the surface of a 3D collagen sponge scaffold with GO dispersion. Scaffolds were characterized using cytotoxicity and tissue reactivity tests. In addition, GO scaffold was implanted into dog class II furcation defects and periodontal healing was investigated at 4 weeks postsurgery. GO scaffold exhibited low cytotoxicity and enhanced cellular ingrowth behavior and rat bone forming ability. In addition, GO scaffold stimulated healing of dog class II furcation defects. Periodontal attachment formation, including alveolar bone, periodontal ligament-like tissue, and cementum-like tissue, was significantly increased by GO scaffold implantation, compared with untreated scaffold. The results suggest that GO scaffold is biocompatible and possesses excellent bone and periodontal tissue formation ability. Therefore, GO scaffold would be beneficial for periodontal tissue engineering therapy.

Suture anchor fixation strength with or without augmentation in osteopenic and severely osteoporotic bones in rotator cuff repair: a biomechanical study on polyurethane foam model

PubMed Central

2014-01-01

Background The purpose of the present study was to compare the results of various types of anchor applications with or without augmentation in both osteopenic and severely osteoporotic bone models. Methods Two different types of suture anchors were tested in severely osteoporotic (SOP) and osteopenic polyurethane (PU) foam blocks using an established protocol. An Instron machine applied static loading parallel to the axis of insertion until failure, and the mean anchor failure strengths were calculated. The mode of failure (anchor pullout, suture tear) was recorded. The anchors tested included the Corkscrew® (CS) (Arthrex Inc., Naples, FL, USA) (without augmentation, polymethylmethacrylate (PMMA)-augmented, and bioabsorbable tricalcium phosphate (TCP) cement-augmented) and Corkscrew® FT II (CS FT II) 5.5 mm (without augmentation as used routinely). Results The mean failure loads for both SOP and osteopenic PU foam blocks, respectively, were as follows: CS, 16.2 and 212.4 N; CS with TCP, 75.2 and 396 N; CS with PMMA, 101.2 and 528.8 N; CS FT II, 13.8 and 339.8 N. Conclusions Augmentation of CS with TCP or PMMA would be essential to SOP bones. In the osteopenic bone model, although anchor fixation augmented with PMMA is the best fixation method, CS augmented with TCP cement or CS FT II without any need for augmentation may also be used as an alternative. PMID:25148925

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

PubMed

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

2009-07-01

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

Effect of low-magnitude different-frequency whole-body vibration on subchondral trabecular bone microarchitecture, cartilage degradation, bone/cartilage turnover, and joint pain in rabbits with knee osteoarthritis.

PubMed

Junbo, Wang; Sijia, Liu; Hongying, Chen; Lei, Liu; Pu, Wang

2017-06-15

Whole-body vibration(WBV) has been suggested for the prevention of subchondral bone loss of knee osteoarthritis (OA) . This study examined the effects of different frequency of whole-body vibration on subchondral trabecular bone microarchitecture, cartilage degradation and metabolism of the tibia and femoral condyle bone, and joint pain in an anterior cruciate ligament transection (ACLT)-induced knee osteoarthritisrabbit model. Ninety adult rabbits were divided into six groups: all groups received unilateral ACLT; Group 1, ACLT only; Group 2, 5 Hz WBV; Group 3, 10 Hz WBV; Group 4, 20 Hz WBV; Group 5, 30 Hz WBV; and Group 6, 40 Hz WBV. Pain was tested via weight-bearing asymmetry. Subchondral trabecular bone microarchitecture was examined using in vivo micro-computed tomography. Knee joint cartilage was evaluated by gross morphology, histology, and ECM gene expression level (aggrecan and type II collagen [CTX-II]). Serum bone-specific alkaline phosphatase, N-mid OC, cartilage oligometric protein, CPII, type I collagen, PIIANP, G1/G2 aggrecan levels, and urinary CTX-II were analyzed. After 8 weeks of low-magnitude WBV, the lower frequency (10 Hz and 20 Hz) WBV treatment decreased joint pain and cartilage resorption, accelerated cartilage formation, delayed cartilage degradation especially at the 20 Hz regimen. However, the higher frequencies (30 Hz and 40 Hz) had worse effects, with worse limb function and cartilage volume as well as higher histological scores and cartilage resorption. In contrast, both prevented loss of trabeculae and increased bone turnover. No significant change was observed in the 5 Hz WBV group. Our data demonstrate that the lower frequencies (10 Hz and 20 Hz) of low-magnitude WBV increased bone turnover, delayed cartilage degeneration, and caused a significant functional change of the OA-affected limb in ACLT-induced OA rabbit model but did not reverse OA progression after 8 weeks of treatment.

Oral administration of undenatured native chicken type II collagen (UC-II) diminished deterioration of articular cartilage in a rat model of osteoarthritis (OA).

PubMed

Bagi, C M; Berryman, E R; Teo, S; Lane, N E

2017-12-01

The aim of this study was to determine the ability of undenatured native chicken type II collagen (UC-II) to prevent excessive articular cartilage deterioration in a rat model of osteoarthritis (OA). Twenty male rats were subjected to partial medial meniscectomy tear (PMMT) surgery to induce OA. Immediately after the surgery 10 rats received vehicle and another 10 rats oral daily dose of UC-II at 0.66 mg/kg for a period of 8 weeks. In addition 10 naïve rats were used as an intact control and another 10 rats received sham surgery. Study endpoints included a weight-bearing capacity of front and hind legs, serum biomarkers of bone and cartilage metabolism, analyses of subchondral and cancellous bone at the tibial epiphysis and metaphysis, and cartilage pathology at the medial tibial plateau using histological methods. PMMT surgery produced moderate OA at the medial tibial plateau. Specifically, the deterioration of articular cartilage negatively impacted the weight bearing capacity of the operated limb. Immediate treatment with the UC-II preserved the weight-bearing capacity of the injured leg, preserved integrity of the cancellous bone at tibial metaphysis and limited the excessive osteophyte formation and deterioration of articular cartilage. Study results demonstrate that a clinically relevant daily dose of UC-II when applied immediately after injury can improve the mechanical function of the injured knee and prevent excessive deterioration of articular cartilage. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Highly efficient nuclear DNA typing of the World War II skeletal remains using three new autosomal short tandem repeat amplification kits with the extended European Standard Set of loci

PubMed Central

Zupanič Pajnič, Irena; Gornjak Pogorelc, Barbara; Balažic, Jože; Zupanc, Tomaž; Štefanič, Borut

2012-01-01

Aim To perform an efficiency study of three new amplification kits with the extended European Standard Set (ESS) of loci for autosomal short tandem repeat (STR) typing of skeletal remains excavated from the World War II mass graves in Slovenia. Methods In the beginning of the 2011, we analyzed 102 bones and teeth using the PowerPlex ESX 17 System (Promega), AmpFiSTR NGM PCR Amplification Kit (Applied Biosystems), and Investigator ESSplex Kit (Qiagen). We cleaned the bones and teeth, removed surface contamination, and ground them into a powder using liquid nitrogen. Prior to DNA isolation with Biorobot EZ1 (Qiagen), 0.5 g bone or tooth powder was decalcified. Nuclear DNA of the samples was quantified using real-time polymerase chain reaction. All three kits used the same extract with the amplification conditions recommended by the manufacturers. Results We extracted up to 131 ng DNA/g of powder from the bones and teeth. All three amplification kits showed very similar efficiency, since DNA typing was successful with all amplification kits in 101 out of 102 bones and teeth, which represents a 99% success rate. Conclusion The commercially available ESX 17, ESSplex, and NGM kits are highly reliable for STR typing of World War II skeletal remains with the DNA extraction method optimized in our laboratory. PMID:22351574

21 CFR 888.3353 - Hip joint metal/ceramic/polymer semi-constrained cemented or nonporous uncemented prosthesis.

Code of Federal Regulations, 2011 CFR

2011-04-01

... fixed in the intramedullary canal of the femur by impaction with or without use of bone cement. The... nonporous metal alloys, and used with or without bone cement. (b) Classification. Class II. [54 FR 48239...

21 CFR 888.3353 - Hip joint metal/ceramic/polymer semi-constrained cemented or nonporous uncemented prosthesis.

Code of Federal Regulations, 2013 CFR

2013-04-01

... fixed in the intramedullary canal of the femur by impaction with or without use of bone cement. The... nonporous metal alloys, and used with or without bone cement. (b) Classification. Class II. [54 FR 48239...

21 CFR 888.3353 - Hip joint metal/ceramic/polymer semi-constrained cemented or nonporous uncemented prosthesis.

Code of Federal Regulations, 2014 CFR

2014-04-01

... fixed in the intramedullary canal of the femur by impaction with or without use of bone cement. The... nonporous metal alloys, and used with or without bone cement. (b) Classification. Class II. [54 FR 48239...

21 CFR 888.3353 - Hip joint metal/ceramic/polymer semi-constrained cemented or nonporous uncemented prosthesis.

Code of Federal Regulations, 2012 CFR

2012-04-01

... fixed in the intramedullary canal of the femur by impaction with or without use of bone cement. The... nonporous metal alloys, and used with or without bone cement. (b) Classification. Class II. [54 FR 48239...

21 CFR 888.3353 - Hip joint metal/ceramic/polymer semi-constrained cemented or nonporous uncemented prosthesis.

Code of Federal Regulations, 2010 CFR

2010-04-01

... fixed in the intramedullary canal of the femur by impaction with or without use of bone cement. The... nonporous metal alloys, and used with or without bone cement. (b) Classification. Class II. [54 FR 48239...

Evaluation of calabash chalk effect on femur bone morphometry and mineralization in young wistar rats: A pilot study.

PubMed

Ekong, Moses B; Ekanem, Theresa B; Sunday, Abraham O; Aquaisua, Aquaisua N; Akpanabiatu, Monday I

2012-07-01

Calabash chalk, a popularly consumed geophagic material in Nigeria has been reported to contain lead, arsenic, alpha lindane, endrin, and endosulfan 11 among other pollutants. The continuous exposure of young children to this chalk necessitated this study on the bone morphometry and mineralization in young Wistar rats. Fourteen young (weanling) Wistar rats of both sexes weighing 54-72 g were assigned into two groups of seven animals each. Group I served as control, while group II was the test group (TG). 40 mg/ml of C. chalk was administered as suspension to the test animals in group II. Animals in the control group were orally treated with 1ml of distilled water. Administration of the C. chalk in the animals lasted for 28 days, and the animals were sacrificed on day 29, using chloroform anaesthesia. The femur bones were dissected out, cleaned of flesh and sun-dried. The lengths and weights of the femur bones were measured using graphite furnace atomic mass spectrophotometer. Results showed 1.6% decrease in body weight change in the TG, insignificant decreases in the weights and lengths of both the right and left femur bones, and significant decreased (P < 0.0126) organ-somatic index, and femur bones concentrations (mg/l) of zinc, phosphate, carbonate, calcium, sodium, and potassium (P < 0.05). In conclusion, this study showed that C. chalk may alter growth rate, and cause de-mineralization in the femur bone, hence, it may be detrimental to bone growth.

A study on Rayleigh wave dispersion in bone according to Mindlin's Form II gradient elasticity.

PubMed

Vavva, Maria G; Gergidis, Leonidas N; Protopappas, Vasilios C; Charalambopoulos, Antonios; Polyzos, Demosthenes; Fotiadis, Dimitrios I

2014-05-01

The classical elasticity cannot effectively describe bone's mechanical behavior since only homogeneous media and local stresses are assumed. Additionally, it cannot predict the dispersive nature of the Rayleigh wave which has been reported in experimental studies and was also demonstrated in a previous computational study by adopting Mindlin's Form II gradient elasticity. In this work Mindlin's theory is employed to analytically determine the dispersion of Rayleigh waves in a strain gradient elastic half-space. An isotropic semi-infinite space is considered with properties equal to those of bone and dynamic behavior suffering from microstructural effects. Microstructural effects are considered by incorporating four intrinsic parameters in the stress analysis. The results are presented in the form of group and phase velocity dispersion curves and compared with existing computational results and semi-analytical curves calculated for a simpler case of Rayleigh waves in dipolar gradient elastic half-spaces. Comparisons are also performed with the velocity of the first-order antisymmetric mode propagating in a dipolar plate so as to observe the Rayleigh asymptotic behavior. It is shown that Mindlin's Form II gradient elasticity can effectively describe the dispersive nature of Rayleigh waves. This study could be regarded as a step toward the ultrasonic characterization of bone.

Acemannan sponges stimulate alveolar bone, cementum and periodontal ligament regeneration in a canine class II furcation defect model.

PubMed

Chantarawaratit, P; Sangvanich, P; Banlunara, W; Soontornvipart, K; Thunyakitpisal, P

2014-04-01

Periodontal disease is a common infectious disease, found worldwide, causing the destruction of the periodontium. The periodontium is a complex structure composed of both soft and hard tissues, thus an agent applied to regenerate the periodontium must be able to stimulate periodontal ligament, cementum and alveolar bone regeneration. Recent studies demonstrated that acemannan, a polysaccharide extracted from Aloe vera gel, stimulated both soft and hard tissue healing. This study investigated effect of acemannan as a bioactive molecule and scaffold for periodontal tissue regeneration. Primary human periodontal ligament cells were treated with acemannan in vitro. New DNA synthesis, expression of growth/differentiation factor 5 and runt-related transcription factor 2, expression of vascular endothelial growth factor, bone morphogenetic protein-2 and type I collagen, alkaline phosphatase activity, and mineralized nodule formation were determined using [(3)H]-thymidine incorporation, reverse transcription-polymerase chain reaction, enzyme-linked immunoabsorbent assay, biochemical assay and alizarin red staining, respectively. In our in vivo study, premolar class II furcation defects were made in four mongrel dogs. Acemannan sponges were applied into the defects. Untreated defects were used as a negative control group. The amount of new bone, cementum and periodontal ligament formation were evaluated 30 and 60 d after the operation. Acemannan significantly increased periodontal ligament cell proliferation, upregulation of growth/differentiation factor 5, runt-related transcription factor 2, vascular endothelial growth factor, bone morphogenetic protein 2, type I collagen and alkaline phosphatase activity, and mineral deposition as compared with the untreated control group in vitro. Moreover, acemannan significantly accelerated new alveolar bone, cementum and periodontal ligament formation in class II furcation defects. Our data suggest that acemannan could be a candidate biomolecule for periodontal tissue regeneration. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Generation of novel bone forming cells (monoosteophils) from the cathelicidin-derived peptide LL-37 treated monocytes.

PubMed

Zhang, Zhifang; Shively, John E

2010-11-15

Bone generation and maintenance involve osteoblasts, osteoclasts, and osteocytes which originate from unique precursors and rely on key growth factors for differentiation. However, an incomplete understanding of bone forming cells during wound healing has led to an unfilled clinical need such as nonunion of bone fractures. Since circulating monocytes are often recruited to sites of injury and may differentiate into various cell types including osteoclasts, we investigated the possibility that circulating monocytes in the context of tissue injury may also contribute to bone repair. In particular, we hypothesized that LL-37 (produced from hCAP-18, cathelicidin), which recruits circulating monocytes during injury, may play a role in bone repair. Treatment of monocytes from blood with LL-37 for 6 days resulted in their differentiation to large adherent cells. Growth of LL-37-differentiated monocytes on osteologic discs reveals bone-like nodule formation by scanning electron microscopy (SEM). In vivo transplantation studies in NOD/SCID mice show that LL-37-differentiated monocytes form bone-like structures similar to endochondral bone formation. Importantly, LL-37-differentiated monocytes are distinct from conventional monocyte-derived osteoclasts, macrophages, and dendritic cells and do not express markers of the mesenchymal stem cells (MSC) lineage, distinguishing them from the conventional precursors of osteoblasts. Furthermore, LL-37 differentiated monocytes express intracellular proteins of both the osteoblast and osteoclast lineage including osteocalcin (OC), osteonectin (ON), bone sialoprotein II (BSP II), osteopontin (OP), RANK, RANKL, MMP-9, tartrate resistant acid phosphatase (TRAP), and cathepsin K (CK). Blood derived monocytes treated with LL-37 can be differentiated into a novel bone forming cell that functions both in vitro and in vivo. We propose the name monoosteophil to indicate their monocyte derived lineage and their bone forming phenotype. These cells may have wide ranging implications in the clinic including repair of broken bones and treatment of osteoporosis.

Does the use of ACE inhibitors or angiotensin receptor blockers affect bone loss in older men?

PubMed Central

Leung, J.; Zhang, Y. F.; Bauer, D.; Ensrud, K. E.; Barrett-Connor, E.; Leung, P. C.

2013-01-01

Summary In a prospective cohort study of 5,995 older American men (MrOS), users of angiotensin-converting enzyme (ACE) inhibitors had a small but significant increase in bone loss at the hip over 4 years after adjustment for confounders. Use of angiotensin II AT1 receptor blockers (ARB) was not significantly associated with bone loss. Introduction Experimental evidence suggests that angiotensin II promotes bone loss by its effects on osteoblasts. It is therefore plausible that ACE inhibitor and ARB may reduce rates of bone loss. The objective of this study is to examine the independent effects of ACE inhibitor and ARB on bone loss in older men. Methods Out of 5,995 American men (87.2%) aged ≥65 years, 5,229 were followed up for an average of 4.6 years in a prospective six-center cohort study—The Osteoporotic Fractures in Men Study (MrOS). Bone mineral densities (BMD) at total hip, femoral neck, and trochanter were measured by Hologic densitometer (QDR 4500) at baseline and year 4. Results Out of 3,494 eligible subjects with complete data, 1,166 and 433 subjects reported use of ACE inhibitors and ARBs, respectively. When compared with nonusers, continuous use of ACE inhibitors was associated with a small (0.004 g/cm2) but significant increase in the average rate of BMD loss at total hip and trochanter over 4 years after adjustment for confounders. Use of ARB was not significantly associated with bone loss. Conclusion Use of ACE inhibitors but not ARB may marginally increase bone loss in older men. PMID:22080379

Functionalization of deproteinized bovine bone with a coating-incorporated depot of BMP-2 renders the material efficiently osteoinductive and suppresses foreign-body reactivity.

PubMed

Wu, Gang; Hunziker, Ernst B; Zheng, Yuanna; Wismeijer, Daniel; Liu, Yuelian

2011-12-01

The repair of critical-sized bony defects remains a challenge in the fields of implantology, maxillofacial surgery and orthopaedics. As an alternative bone-defect filler to autologous bone grafts, deproteinized bovine bone (DBB) is highly osteoconductive and clinically now widely used. However, this product suffers from the disadvantage of not being intrinsically osteoinductive. In the present study, this property was conferred by coating DBB with a layer of calcium phosphate into which bone morphogenetic protein 2 (BMP-2) was incorporated. Granules of DBB bearing a coating-incorporated depot of BMP-2--together with the appropriate controls (DBB bearing a coating but no BMP-2; uncoated DBB bearing adsorbed BMP-2; uncoated DBB bearing no BMP-2)--were implanted subcutaneously in rats. Five weeks later, the implants were withdrawn for a histomorphometric analysis of the volume densities of (i) bone, (ii) bone marrow, (iii) foreign-body giant cells and (iv) fibrous capsular tissue. Parameters (i) and (ii) were highest, whilst parameters (iii) and (iv) were lowest in association with DBB bearing a coating-incorporated depot of BMP-2. Hence, this mode of functionalization not only confers DBB with the property of osteoinductivity but also improves its biocompatibility--thus dually enhancing its clinical potential in the repair of bony defects. Copyright © 2011 Elsevier Inc. All rights reserved.

Effects of boning method and postmortem aging on meat quality characteristics of pork loin.

PubMed

Li, Chunbao; Wu, Juqing; Zhang, Nan; Zhang, Song; Liu, Juan; Li, Jinping; Li, Hongmin; Feng, Xianchao; Han, Yanqing; Zhu, Zhiyuan; Xu, Xinglian; Zhou, Guanghong

2009-10-01

This work investigated the effects of boning method and postmortem aging on pork loin color, shearing value and sensory attributes. Two experiments were assigned. In Experiment I, 30 Chinese native black pigs were slaughtered and their carcasses were divided into three groups: (i) hot-boning: carcasses were fabricated within 45 min postmortem just after dressing; (ii) cold boning at 24 h: carcasses were fabricated after chilling at 0 degrees C for 24 h; (iii) cold boning at 36 h: carcasses were fabricated after chilling at 0 degrees C for 36 h. In Experiment II, right sides of the second group in Experiment I were used and primal cuts were vacuum packed and aged for 1 day, 8 days and 16 days. Pork loins (Longissimus lumborum) were used for color measurement, shearing test, and sensory evaluation. Among three boning methods, cold-boning at 36 h postmortem had the advantages of giving muscles a better color, the lowest cooking loss and cooked shearing value, and the highest sensory tenderness, juiciness, flavor and overall liking. Postmortem aging could improve pork quality characteristics, but it is not the fact that the longer aging time is, the better pork quality would be. Eight days may be enough to obtain an acceptable sensory attribute. These results are meaningful for pork processing and pork consumption.

Treatment of Class II malocclusion with mandibular skeletal anchorage.

PubMed

Cakir, Ezgi; Malkoç, Siddik; Kirtay, Mustafa

2017-06-01

The aim of this case report was to present the dentofacial changes obtained with bone anchorage in a Class II patient with moderate to severe crowding. A boy, aged 14.5 years, with a dolichofacial type, convex profile, and skeletal and dental Class II relationships was examined. After evaluation, functional treatment with bone anchorage and 4 first premolar extractions was decided as the treatment approach. Miniplates were placed on the buccal shelves of the mandibular third molars. The hook of the anchor was revealed from the first molar level. After surgery, the 4 first premolars were extracted to retract the protrusive mandibular incisors. The maxillary and mandibular first molars were banded, and a lip bumper was inserted to apply elastics and to help distalize the maxillary first molars. Orthodontic forces of 300 to 500 g were applied immediately after placement, originating from the miniscrews to the hooks of the appliance to advance the mandible. After 20 months of treatment, the patient had a dental and skeletal Class I relationship, the mandible was advanced, the maxilla was restrained, and overjet was decreased. The combination of a bone anchor, Class II elastics, and an inner bow is a promising alternative to functional treatment, along with extractions, in Class II patients. Copyright © 2016 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Increased activity of osteocyte autophagy in ovariectomized rats and its correlation with oxidative stress status and bone loss

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

Yang, Yuehua, E-mail: yuesjtu@126.com; Zheng, Xinfeng, E-mail: zxf272@126.com; Li, Bo, E-mail: libo@126.com

Highlights: • Examine autophagy level in the proximal tibia of ovariectomized rats. • Investigate whether autophagy level is associated with bone loss. • Investigate whether autophagy level is associated with oxidative stress status. - Abstract: Objectives: The objectives of the present study were to investigate ovariectomy on autophagy level in the bone and to examine whether autophagy level is associated with bone loss and oxidative stress status. Methods: 36 female Sprague–Dawley rats were randomly divided into sham-operated (Sham), and ovariectomized (OVX) rats treated either with vehicle or 17-β-estradiol. At the end of the six-week treatment, bone mineral density (BMD) andmore » bone micro-architecture in proximal tibias were assessed by micro-CT. Serum 17β-estradiol (E2) level were measured. Total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity, catalase (CAT) activity in proximal tibia was also determined. The osteocyte autophagy in proximal tibias was detected respectively by Transmission Electron Microscopy (TEM), immunofluorescent histochemistry (IH), realtime-PCR and Western blot. In addition, the spearman correlation between bone mass, oxidative stress status, serum E2 and autophagy were analyzed. Results: Ovariectomy increased Atg5, LC3, and Beclin1 mRNA and proteins expressions while decreased p62 expression. Ovariectomy also declined the activities of T-AOC, CAT, and SOD. Treatment with E2 prevented the reduction in bone mass as well as restored the autophagy level. Furthermore, LC3-II expression was inversely correlated with T-AOC, CAT, and SOD activities. A significant inverse correlation between LC3-II expression and BV/TV, Tb.N, BMD in proximal tibias was found. Conclusions: Ovariectomy induced oxidative stress, autophagy and bone loss. Autophagy of osteocyte was inversely correlated with oxidative stress status and bone loss.« less

Genetics Home Reference: Czech dysplasia

MedlinePlus

... for making a protein that forms type II collagen. This type of collagen is found mostly in the clear gel that ... in the nose and external ears. Type II collagen is essential for the normal development of bones ...

Genetics Home Reference: achondrogenesis

MedlinePlus

... for making a protein that forms type II collagen. This type of collagen is found mostly in cartilage and in the ... gene interfere with the assembly of type II collagen molecules, which prevents bones and other connective tissues ...

Genetics Home Reference: Kniest dysplasia

MedlinePlus

... for making a protein that forms type II collagen. This type of collagen is found mostly in the clear gel that ... in the nose and external ears. Type II collagen is essential for the normal development of bones ...

Genetics Home Reference: hypochondrogenesis

MedlinePlus

... for making a protein that forms type II collagen. This type of collagen is found mostly in the clear gel that ... in the nose and external ears. Type II collagen is essential for the normal development of bones ...

Changes consequent to maxillary molar distalization with the bone-anchored pendulum appliance.

PubMed

Cambiano, Aldo Otazú; Janson, Guilherme; Fuziy, Acácio; Garib, Daniela Gamba; Lorenzoni, Diego Coelho

2017-01-01

This retrospective study aimed to evaluate the dentoalveolar, skeletal, and soft tissue effects obtained with bone-anchored pendulum appliance in patients with Class II malocclusion. A total of 18 patients (4 male, 14 female) at a mean pretreatment age of 14.0 years (+1.08) were enrolled in this study. All patients were treated with the bone-anchored pendulum appliance for an average duration of 4.8 months. Only the active distalization period was evaluated with predistalization and postdistalization lateral cephalograms. Skeletal, dentoalveolar, and soft tissue variables were obtained. Based on these variables, the treatment effects were evaluated with dependent t -test. Correction of Class II molar relationship resulted from distal movement of 3.45 mm and tipping of 11.24° of the first maxillary molars. The premolars were distalized accompanying the molars. The bone-anchored pendulum appliance proved to be an effective method for distalization of maxillary molars in cases that require maximum anchorage, avoiding reciprocal mesial movement of premolars and incisors.

[CIP and CAP fragments of parathormone and selected parameters of calcium-phosphate balance in patients with chronic kidney disease treated with repeated haemodialysis].

PubMed

Polak-Jonkisz, Dorota; Zwolińska, Danuta; Nahaczewska, Wiesława

2010-01-01

Chronic kidney disease (CKD) leads to bone and mineral complications, which are manifested, among others, by hyperparathyroidism, calcium-phosphate and vitamin D balance disturbances. The results of investigation assessing the usefulness of CAP/CIP ratio, (cyclase activating PTH/cyclase inactive PTH) as a marker of bone turnover and bone disturbances in this group of patients are contradictory. was to estimate the concentration of CAP and CIP of parathormone, connection with selected calcium-phosphate balance parameters and usefulness of CAP/CIP ratio to differentiate bone mineral density in patients with CKD treated with repeated haemodialysis. The study included 31 children aged 5 to 18 years. Group I - 15 haemodialysed children. Group II - 16 healthy children. The patients underwent the following serum measurements: calcium concentration (Ca), inorganic phosphate (P), 1.25-dihydroxyvitamin D, parathormone (intact PTH), and CAP, CIP were evaluated with Scantibodies Laboratory Inc test. In group I the densitometric examination was done using the Lunar DPX-L system, performing the overall bone measurement. In children from group I the average values of iPTH concentration and both CIP and CAP components were significantly elevated (p<0.05) as compared to group II. CAP/CIP ratio in group I was <1; in healthy children >1. Average concentrations of Ca and 1.25(OH)2D in serum of group I were lowered, although without statistical significance in comparison with group II. CAP/CIP ratio does not differentiate the children with bone disturbances. Densitometric examination revealed osteopenic changes in 3 children and osteoporosis in 2 children. There were no statistically significant correlations between the examined parameters. 1. The CIP/CAP ratio does not differentiate the bone mineral density status and it is not associated with biochemical parameters of calcium-phosphate metabolism. 2. This indicates its poor diagnostic utility with reference to mineralization disturbances in children with chronic kidney disease.

Increased cartilage type II collagen degradation in patients with osteogenesis imperfecta used as a human model of bone type I collagen alterations.

PubMed

Rousseau, Jean-Charles; Chevrel, Guillaume; Schott, Anne-Marie; Garnero, Patrick

2010-04-01

We investigated whether cartilage degradation is altered in adult patients with mild osteogenesis imperfecta (OI) used as a human model of bone type I collagen-related osteoarthritis (OA). Sixty-four adult patients with OI (39% women, mean age+/-SD: 37+/-12 years) and 64 healthy age-matched controls (54% women, 39+/-7 years) were included. We also compared data in 87 patients with knee OA (73% women, 63+/-8 years, mean disease duration: 6 years) and 291 age-matched controls (80% women, 62+/-10 years). Urinary C-terminal cross-linked telopeptide of type II collagen (CTX-II), a marker of cartilage degradation, urinary helical peptide of type I collagen (Helix-I), a marker of bone resorption, and the urinary ratio between non-isomerised/isomerised (alpha/beta CTX-I) type I collagen C-telopeptide, a marker of type I collagen maturation, were measured. Patients with OI had CTX-II levels similar to those of subjects with knee OA (p=0.89; mean+/-SEM; 460+/-57 ng/mmol Cr for OI group and 547+/-32 ng/mmol Cr for OA group) and significantly higher than both young (144+/-7.8 ng/mmol Cr, p<0.0001) and old controls (247+/-7 ng/mmol Cr, p<0.0001). In patients with OI, increased Helix-I (p<0.0001) and alpha/beta CTX-I (p=0.0067) were independently associated with increased CTX-II and together explained 26% of its variance (p< 0.0001). In patients with knee OA, increased levels of alpha/beta CTX-I ratio were also associated with higher CTX-II levels. Adult patients with OI or knee OA are characterized by increased cartilage type II collagen degradation, which is associated with increased type I collagen degradation for OI and lower type I collagen maturation for both OI and OA. These data suggest that both quantitative and qualitative alterations of bone type I collagen metabolism are involved in increased cartilage degradation in patients with OI or knee OA. Copyright 2009 Elsevier Inc. All rights reserved.

Design and characterization of a composite material based on Sr(II)-loaded clay nanotubes included within a biopolymer matrix.

PubMed

Del Buffa, Stefano; Bonini, Massimo; Ridi, Francesca; Severi, Mirko; Losi, Paola; Volpi, Silvia; Al Kayal, Tamer; Soldani, Giorgio; Baglioni, Piero

2015-06-15

This paper reports on the preparation, characterization, and cytotoxicity of a hybrid nanocomposite material made of Sr(II)-loaded Halloysite nanotubes included within a biopolymer (3-polyhydroxybutyrate-co-3-hydroxyvalerate) matrix. The Sr(II)-loaded inorganic scaffold is intended to provide mechanical resistance, multi-scale porosity, and to favor the in-situ regeneration of bone tissue thanks to its biocompatibility and bioactivity. The interaction of the hybrid system with the physiological environment is mediated by the biopolymer coating, which acts as a binder, as well as a diffusional barrier to the Sr(II) release. The degradation of the polymer progressively leads to the exposure of the Sr(II)-loaded Halloysite scaffold, tuning its interaction with osteogenic cells. The in vitro biocompatibility of the composite was demonstrated by cytotoxicity tests on L929 fibroblast cells. The results indicate that this composite material could be of interest for multiple strategies in the field of bone tissue engineering. Copyright © 2015 Elsevier Inc. All rights reserved.

Metabolic bone disease in chronic renal failure. II. Renal transplant patients.

PubMed Central

Huffer, W. E.; Kuzela, D.; Popovtzer, M. M.; Starzl, T. E.

1975-01-01

Trabecular vertebral bone of renal transplant patients was quantitatively compared with bone from normal individuals and dialyzed and nondialyzed patienets with chronic renal failure reported in detail in an earlier study. Long- and short-term transplant patients have increased bone resorption and mineralization defects similar to renal osteodystrophy in dialyzed and nondialyzed patients. However, in transplant patients the magnitude of resorption is greater, and bone volume tends to decrease rather than increase. Resorptive activity in transplant patients is maximal during the first year after transplantation. Bone volume decreases continuously for at least 96 months after transplantation. Only decreased bone volume correlated with success or failure of the renal transplant. Morphologic findings in this study correlate with other clinical and morphologic data to suggest that reduction in bone volume in transplant patients results from a combination of persistent hyperparathyroidism and suppression of bone formation by steroid therapy. Images Fig 1 PMID:1091152

Continuous decompression of unicameral bone cyst with cannulated screws: a comparative study.

PubMed

Brecelj, Janez; Suhodolcan, Lovro

2007-09-01

We determined the role of mechanical decompression in the resolution of unicameral bone cyst. A total of 69 children with unicameral bone cysts were treated either by (i) open curettage and bone grafting, (ii) steroid injection or (iii) cannulated screw insertion. During a mean follow-up of 69 months (range, 12-58), the cysts were evaluated by radiological criteria. The healing rates in the three groups were 25, 12 and 29% after the first treatment, and a further 50, 19 and 65% after the second. The study has demonstrated the advantages of the decompression technique for unicameral bone cysts over other treatment modalities studied.

Molecular changes after shockwave therapy in osteoarthritic knee in rats

NASA Astrophysics Data System (ADS)

Wang, C.-J.; Sun, Y.-C.; Wu, C.-T.; Weng, L.-H.; Wang, F.-S.

2016-01-01

This study investigated the molecular changes of DKK-1, MMP13, Wnt-5a and \\upbeta -catenin after extracorporeal shockwave therapy (ESWT) in anterior cruciate ligament transected (ACLT) osteoarthritic (OA) knee in rats. 27 male Spraque-Dawley rats were divided into three groups. Group I was the control one and received sham knee arthrotomy but no ACLT or ESWT. Group II underwent ACLT, but no ESWT. Group III underwent ACLT and received ESWT. The animals were killed at 12 weeks, and the harvested knee specimens were subjected to histopathological examination and immunohistochemical analysis. Radiographs of the knees were obtained at 0 and 12 weeks. At 12 weeks, radiographs of group II showed more arthritic changes with formation of osteochondral fragments, whereas very subtle arthritis was noted in groups I and III. In histopathological examination, group II showed a significant increase of Mankin score and a decrease of subchondral bone as compared to groups I and III. Group III showed a significant decrease of Mankin score and an increase of subchondral bone, with the data comparable to group I. In immunohistochemical analysis, group II showed significant increases of DKK-1 and MMP13 and decreases of Wnt-5a and \\upbeta -catenin in articular cartilage and subchondral bone as compared to groups I and III. Group III showed significant decreases of DKK-1 and MMP13 and increases of Wnt-5a and \\upbeta -catenin, with the data comparable to group I. In conclusion, the application of ESWT causes molecular changes that are consistent with the improvement in subchondral bone remodeling and chondroprotective effect in ACLT OA knees in rats.

Odanacatib, a New Drug for the Treatment of Osteoporosis: Review of the Results in Postmenopausal Women

PubMed Central

Pérez-Castrillón, José Luis; Pinacho, Florentino; De Luis, Daniel; Lopez-Menendez, María; Dueñas Laita, Antonio

2010-01-01

Osteoclasts are specialized cells that initiate the process of bone resorption, which has two phases, dissolution of the mineral component and degradation of the organic matrix, in which cathepsin K plays a key role. Cathepsin K inhibitors, which block the activity of cathepsin on bone resorption lacunae, may be a new therapeutic option in osteoporosis. Odanacatib is a nonpeptidic biaryl inhibitor of cathepsin K. Two studies have evaluated the efficacy and safety of odanacatib, a phase I study to determine the dose and a phase II study of safety and efficacy. Due to the long half-life of odanacatib and the similar effects of different doses on bone remodeling markers, a weekly dosage was chosen for the phase II trail, with the best results being obtained with a dose of 50 mg. At 36 months, increases in bone mineral density similar to those produced by other powerful antiresorptive drugs (zoledronate and denosumab) were observed but there were differences in the behaviour of bone remodeling markers. Data on fractures from the phase III trial currently in development are required to confirm these possible advantages. PMID:20948576

Characterization and evaluation of graphene oxide scaffold for periodontal wound healing of class II furcation defects in dog

PubMed Central

Kawamoto, Kohei; Miyaji, Hirofumi; Nishida, Erika; Miyata, Saori; Kato, Akihito; Tateyama, Akito; Furihata, Tomokazu; Shitomi, Kanako; Iwanaga, Toshihiko; Sugaya, Tsutomu

2018-01-01

Introduction The 3-dimensional scaffold plays a key role in volume and quality of repair tissue in periodontal tissue engineering therapy. We fabricated a novel 3D collagen scaffold containing carbon-based 2-dimensional layered material, named graphene oxide (GO). The aim of this study was to characterize and assess GO scaffold for periodontal tissue healing of class II furcation defects in dog. Materials and methods GO scaffolds were prepared by coating the surface of a 3D collagen sponge scaffold with GO dispersion. Scaffolds were characterized using cytotoxicity and tissue reactivity tests. In addition, GO scaffold was implanted into dog class II furcation defects and periodontal healing was investigated at 4 weeks postsurgery. Results GO scaffold exhibited low cytotoxicity and enhanced cellular ingrowth behavior and rat bone forming ability. In addition, GO scaffold stimulated healing of dog class II furcation defects. Periodontal attachment formation, including alveolar bone, periodontal ligament-like tissue, and cementum-like tissue, was significantly increased by GO scaffold implantation, compared with untreated scaffold. Conclusion The results suggest that GO scaffold is biocompatible and possesses excellent bone and periodontal tissue formation ability. Therefore, GO scaffold would be beneficial for periodontal tissue engineering therapy. PMID:29713167

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

Culbert, A.A.; Wallis, G.A.; Kadler, K.E.

The brittleness of bone in people with lethal (type II) osteogenesis imperfecta, a heritable disorder caused by mutations in the type I collagen genes, arises from the deposition of abnormal collagen in the bone matrix. The inability of the abnormal collagen to participate in mineralization may be caused by its failure to interact with other bone proteins. Here, we have designed a strategy to isolate the genes important for mineralization of collagen during bone formation. Cells isolated from 16-day embryonic chick calvaria and seeded post-confluence in culture deposited a mineralized matrix over a period of 2 weeks. Chick skin fibroblastsmore » seeded and cultured under the same conditions did not mineralize. Using RT-PCR, we prepared short cDNAs ({approximately}300 bp) corresponding to the 3{prime} ends of mRNA from fibroblasts and separately from the mineralizing calvarial cells. Subtractive cDNA hybridization generated a pool of cDNAs that were specific to mineralizing calvarial cells but not to fibroblasts. Screening of 100,000 plaques of a chick bone ZAP Express cDNA library with this pool of mineralizing-specific cDNAs identified ten clones which comprised full-length cDNAs for the bone proteins osteopontin (eight of the ten positives), bone sialoprotein II (one of the ten positives), and cystatin (one of the ten positives). cDNAs for type I collagen, fibronectin, alkaline phosphatase, house-keeping genes, and other genes expressed in fibroblasts were not identified in this preliminary screen. The pool of short cDNAs is likely to comprise cDNAs for further bone-specific genes and will be used to screen the entire bone cDNA library of 4.2 million clones. 30 refs., 4 figs.« less

An open cohort study of bone metastasis incidence following surgery in breast cancer patients.

PubMed

Koizumi, Mitsuru; Yoshimoto, Masataka; Kasumi, Fujio; Iwase, Takuji

2010-07-21

To help design clinical trials of adjuvant bisphosphonate therapy for breast cancer, the temporal incidence of bone metastasis was investigated in a cohort of patients. We have tried to draw the criteria to use adjuvant bisphosphonate. Consecutive breast cancer patients undergoing surgery between 1988 and 1998 (5459 patients) were followed up regarding bone metastasis until December 2006. Patients' characteristics at the time of surgery were analyzed by Cox's method, with bone metastasis as events. Patient groups were assigned according to Cox's analysis, and were judged either to require the adjuvant bisphosphonate or not, using the tentative criteria: high risk (>3% person-year), medium risk (1-3%), and low risk (<1%). Bone metastasis incidence was constant between 1.0 and 2.8% per person-year more than 10 years. Non-invasive cancer was associated with a very low incidence of bone metastasis (1/436). Multivariate Cox's analysis indicated important factors for bone metastasis were tumor grade (T), nodal grade (pN), and histology. Because T and pN were important factors for bone metastasis prediction, subgroups were made by pTNM stage. Patients at stages IIIA, IIIB and IV had an incidence of >3% per person-year, patients with stage I <1% per person-year, and those with stages II were between 1 and 3%. Further analysis with histology in stage II patients showed that stage IIB with high risk histology also had a high incidence (3% person year), whereas stage IIA with medium risk histology were <1%. Bone metastasis incidence remained constant for many years. Using pN, T, and histopathology, patients could be classified into high, medium, and low risk groups.

Long-term follow-up of callotasis lengthening of the capitate after resection of the lunate for the treatment of stage III lunate necrosis.

PubMed

Hierner, Robert; Wilhelm, Klaus

2010-04-01

The callotasis lengthening technique was used to gradually lengthen the capitate after resection of the lunate in stage IIIa necrosis in 23 patients. Results of ten patients with a follow-up of at least 5 years showed rapid and sufficient callus formation in every patient regardless of age. The callotasis lengthening modification of the Graner II operation provides all advantages and avoids the major inconvenience of the traditional Graner II operation. There was no increased rate of disturbed fracture healing. Results of the DTPA-gadolinium MRI study did not show any significant impairment of vascularization within the region of the capitate bone. With the "intrinsic bone formation," contrary to every other intercarpal arthrodesis at the wrist, there is no need for an additional bone graft.

Adsorption of Hg(II) and Pb(II) ions by nanoscale zero valent iron supported on ostrich bone ash in a fixed-bed column system.

PubMed

Amiri, Mohammad Javad; Abedi-Koupai, Jahangir; Eslamian, Saeid

2017-07-01

In this research, ostrich bone ash (OBA) was modified with nanoscale zerovalent iron (nZVI) particles and applied as a novel composite adsorbent (OBA/nZVI) for dynamic adsorption/reduction of Hg(II) and Pb(II) ions in a fixed-bed column system. Entrapment of nZVI in OBA beads barricades the particles from oxidation and aggregation. The dynamic behavior of metal ions removal by OBA/nZVI was assessed as a function of inlet flow rates, bed height, initial pollutants concentration and pH. The synthesized OBA/nZVI composite was characterized by several physicochemical techniques. Increase in pH and bed height and decrease in flow rates and initial metal concentration resulted in delay of breakthrough time. OBA breakthrough profile is sharper than the OBA/nZVI breakthrough curve for both metal ions and the breakthrough times increase in the order OBA/nZVI-Hg(II) > OBA/nZVI-Pb(II) > OBA-Pb(II) > OBA-Hg(II). Based on the experiment results, redox reaction is expected to occur to a certain extent, as the standard reduction potentials of Hg(II) and Pb(II) are more than that of Fe(II). From a practical point of view, the OBA/nZVI could be applied as a material to remove Hg(II) and Pb(II) ions from natural surface and ground water with a pH value of 5-9.

Diffusion of beta-lactam antibiotics through the porin channels of Escherichia coli K-12.

PubMed Central

Yoshimura, F; Nikaido, H

1985-01-01

Diffusion rates of various beta-lactam antibiotics through the OmpF and OmpC porin channels of Escherichia coli K-12 were measured by the use of reconstituted proteoliposomes. The results can be interpreted on the basis of the gross physicochemical properties of the antibiotics along the following lines. (i) As noted previously (Nikaido et al., J. Bacteriol., 153:232-240, 1983), there was a monotonous dependence of the penetration rate on the hydrophobicity of the molecule among the classical monoanionic beta-lactams, and a 10-fold increase in the octanol-water partition coefficient of the uncharged molecule decreased the penetration rate by a factor of 5 to 6. (ii) Compounds with exceptionally bulky side chains, such as mezlocillin, piperacillin, and cefoperazone, showed much slower penetration rates than expected from their hydrophobicity. (iii) The substituted oxime side chain on the alpha-carbon of the substituent group at position 7 of the cephem nucleus decreased the penetration rate almost by an order of magnitude; this appears to be largely due to the steric effect. (iv) The presence of a methoxy group at position 7 of the cephalosporins also reduced the penetration rate by 20%, probably also due to the steric hindrance. (v) Zwitterionic compounds penetrated very rapidly, and the correlation between the rate and hydrophobicity appeared to be much weaker than with the monoanionic compounds. Imipenem showed the highest permeability among the compounds tested, presumably due, at least in part, to its compact molecular structure. (vi) Compounds with two negative charges penetrated more slowly than did analogs with only one negatively charged group. Among them, only moxalactam, ceftriaxone, and azthreonam showed penetration rates corresponding to, or higher than, 10% of that of imipenem. PMID:2580479

Changes in Mechanical Properties of Rat Bones under Simulated Effects of Microgravity and Radiation†

NASA Astrophysics Data System (ADS)

Walker, Azida H.; Perkins, Otis; Mehta, Rahul; Ali, Nawab; Dobretsov, Maxim; Chowdhury, Parimal

The aim of this study was to determine the changes in elasticity and lattice structure in leg bone of rats which were: 1) under Hind-Limb Suspension (HLS) by tail for 2 weeks and 2) exposed to a total radiation of 10 Grays in 10 days. The animals were sacrificed at the end of 2 weeks and the leg bones were surgically removed, cleaned and fixed with a buffered solution. The mechanical strength of the bone (elastic modulus) was determined from measurement of bending of a bone when under an applied force. Two methodologies were used: i) a 3-point bending technique and ii) classical bending where bending is accomplished keeping one end fixed. Three point bending method used a captive actuator controlled by a programmable IDEA drive. This allowed incremental steps of 0.047 mm for which the force is measured. The data is used to calculate the stress and the strain. In the second method a mirror attached to the free end of the bone allowed a reflected laser beam spot to be tracked. This provided the displacement measurement as stress levels changed. Analysis of stress vs. strain graph together with solution of Euler-Bernoulli equation for a cantilever beam allowed determination of the elastic modulus of the leg bone for (i) control samples, (ii) HLS samples and (iii) HLS samples with radiation effects. To ascertain changes in the bone lattice structure, the bones were cross-sectioned and imaged with a 20 keV beam of electrons in a Scanning Electron Microscope (SEM). A backscattered detector and a secondary electron detector in the SEM provided the images from well-defined parts of the leg bones. Elemental compositions in combination with mechanical properties (elastic modulus and lattice structure) changes indicated weakening of the bones under space-like conditions of microgravity and radiation.

Morphometric assessment of periodontal tissues in relation to periodontal disease in dogs.

PubMed

Kyllar, Michal; Doskarova, Barbora; Paral, Vaclav

2013-01-01

Dimensions of periodontal tissues are thought to predispose to the development of periodontal disease in man and dogs. Several studies have suggested that thin gingiva correlates with an increased incidence of periodontal disease. In this study, we hypothesized that the dimensions of periodontal tissues will vary in different breeds of dogs and could possibly correlate with the incidence of periodontal disease. Forty-two jaws of dogs aged up to 5-years were examined post-mortem and gingival and alveolar bone thickness were measured using methods of transgingival probing and digital calipers, respectively. Dogs were divided into three groups based on their body weight. Group I (< 5.0 kg; n=21), group II (5 to 10 kg; n=11), and group III (10 to 15 kg; n=10). Thickness of gingiva ranged from 0.30-mm to 3.2-mm and was relatively thinner in group I than in group II and III based on the means of ratios comparison. Alveolar bone thickness ranged from 0.27-mm to 4.1-mm and was relatively thinner in group I compared with groups II and III. Our study showed significantly thinner gingiva and alveolar bone in toy breed dogs compared with small and medium-sized breed dogs. Both gingival and alveolar bone dimensions may be predictors for severity of periodontal disease and influence clinical outcome in certain periodontal surgical procedures.

In vitro selection of RNA aptamer specific to Salmonella typhimurium.

PubMed

Han, Seung Ryul; Lee, Seong-Wook

2013-06-28

Salmonella is a major foodborne pathogen that causes a variety of human diseases. Development of ligands directly and specifically binding to the Salmonella will be crucial for the rapid detection of, and thus for efficient protection from, the virulent bacteria. In this study, we identified a RNA aptamer-based ligand that can specifically recognize Salmonella Typhimurium through SELEX technology. To this end, we isolated and characterized an RNase-resistant RNA aptamer that bound to the OmpC protein of Salmonella Typhimurium with high specificity and affinity (Kd ~ 20 nM). Of note, the selected aptamer was found to specifically bind to Salmonella Typhimurium, but neither to Gram-positive bacteria (Staphylococcus aureus) nor to other Gram-negative bacteria (Escherichia coli O157:H7). This was evinced by aptamer-immobilized ELISA and aptamer-linked precipitation experiments. This Salmonella species-specific aptamer could be useful as a diagnostic ligand against pathogen-caused foodborne sickness.

The role of outer membrane in Serratia marcescens intrinsic resistance to antibiotics.

PubMed

Sánchez, L; Ruiz, N; Leranoz, S; Viñas, M; Puig, M

1997-09-01

Three different porins from Serratia marcescens were described. They were named Omp1, Omp2 and Omp3 and their molecular weights were 42, 40 and 39 kDa respectively. Omp2 and Omp3 showed osmoregulation and thermoregulation in a similar way to OmpC and OmpF of Escherichia coli. Permeability coefficients of the outer membrane of this species were calculated following the Zimmermann and Rosselet method. P values were similar to those obtained in Escherichia coli, which suggests that the chromosomal beta-lactamase would play a major role in the resistance of Serratia marcescens to beta-lactam antibiotics. Both MIC values and permeabilities were modified by salycilates and acetylsalycilate. Synergism between the outer membrane and the beta-lactamase was also evaluated. When bacteria grew in the presence of a beta-lactam in the medium, the beta-lactamase accounted for most of the resistance.

[Case-control study on bone setting manipulation for the treatment of over degree II supination-eversion fractures of ankle joint].

PubMed

Qi, Yue-Feng; Chen, Fa-Lin; Bao, Shu-Ren; Li, Cheng-Huan; Zhao, Xing-Wei; Liu, Shi-Ming; Chen, Wen-Xue; Li, Ye; Wang, Peng

2012-08-01

To explore therapeutic effects of bone setting manipulation for the treatment of over degree II supination-eversion fractures of ankle,and analyze manipulative reduction mechanism. From 2005 to 2008, 95 patients with over degree II supination-eversion fractures of ankle were treated respectively by manipulation and operation. There were 43 cases [11 males and 32 females with an average age of (44.95 +/- 12.65) years] in manipulation group, and 2 cases were degree II, 11 cases were degree III, and 30 cases were degree IV. There were 52 cases [21 males and 31 females with an average age of (39.96 +/- 13.28) years] in operative group,and 6 cases were degree II, 18 cases were degree III, and 28 cases were degree IV. Bone setting manipulation and hard splint external fixation were applied to manipulative group. Operative reduction internal fixation was performed in operative group. X-ray was used to evaluate reduction of fracture before and after treatment, 2 months after treatment. Ankle joint function was evaluated according to Olerud-Molander scoring system after 6 months treatment. All patients were followed up with good reduction. Three cases occurred wound complication in operative group, but not in manipulative group. In manipulation group, 19 cases got excellent results, 20 cases good and 4 cases fair; while in operative group, 30 cases got excellent results, 20 cases good and 2 cases poor. There were no significant differences in fracture reduction and ankle joint function recovery between two groups (P > 0.05). Efficacy of operative treatment was better than that of manipulative treatment at degree IV fracture (P < 0.05). Bone setting manipulation is a good method for treating supination-eversion ankle joint fractures, which has advantages of simple and safe operation, reliable efficacy. For ankle join fracture at degree IV, manipulative reduction should be adopted earlier, and operative treatment also necessary

Reconstruction with 3D-printed pelvic endoprostheses after resection of a pelvic tumour.

PubMed

Liang, H; Ji, T; Zhang, Y; Wang, Y; Guo, W

2017-02-01

The aims of this retrospective study were to report the feasibility of using 3D-printing technology for patients with a pelvic tumour who underwent reconstruction. A total of 35 patients underwent resection of a pelvic tumour and reconstruction using 3D-printed endoprostheses between September 2013 and December 2015. According to Enneking's classification of bone defects, there were three Type I lesions, 12 Type II+III lesions, five Type I+II lesions, two Type I+II+III lesions, ten type I+II+IV lesions and three type I+II+III+IV lesions. A total of three patients underwent reconstruction using an iliac prosthesis, 12 using a standard hemipelvic prosthesis and 20 using a screw-rod connected hemipelvic prosthesis. All patients had an en bloc resection. Margins were wide in 15 patients, marginal in 14 and intralesional in six. After a mean follow-up of 20.5 months (6 to 30), 25 patients survived without evidence of disease, five were alive with disease and five had died from metastatic disease. Complications included seven patients with delayed wound healing and two with a dislocation of the hip. None had a deep infection. For the 30 surviving patients, the mean Musculoskeletal Society 93 score was 22.7 (20 to 25) for patients with an iliac prosthesis, 19.8 (15 to 26) for those with a standard prosthesis, and 17.7 (9 to 25) for those with a screw-rod connected prosthesis. The application of 3D-printing technology can facilitate the precise matching and osseointegration between implants and the host bone. We found that the use of 3D-printed pelvic prostheses for reconstruction of the bony defect after resection of a pelvic tumour was safe, without additional complications, and gave good short-term functional results. Cite this article: Bone Joint J 2017;99-B:267-75. ©2017 The British Editorial Society of Bone & Joint Surgery.

Characterization of collagen II fibrils containing biglycan and their effect as a coating on osteoblast adhesion and proliferation.

PubMed

Douglas, Timothy; Heinemann, Sascha; Hempel, Ute; Mietrach, Carolin; Knieb, Christiane; Bierbaum, Susanne; Scharnweber, Dieter; Worch, Hartmut

2008-04-01

Collagen has been used as a coating material for titanium-based implants for bone contact and as a component of scaffolds for bone tissue engineering. In general collagen type I has been used, however very little attention has been focussed on collagen type II. Collagen-based coatings and scaffolds have been enhanced by the incorporation of the glycosaminoglycan chondroitin sulphate (CS), however the proteglycan biglycan, which is found in bone and contains glycosaminoglycan chains consisting of CS, has not been used as a biomaterial component. The study had the following aims: firstly, five different collagen II preparations were compared with regard to their ability to bind CS and biglycan and the changes in fibril morphology thereby induced. Secondly, the effects of biglycan on the adhesion of primary rat osteoblasts (rO) as well as the proliferation of rO, primary human osteoblasts (hO) and the osteoblast-like cell line 7F2 were studied by culturing the cells on surfaces coated with collagen II fibrils containing biglycan. Fibrils of the collagen II preparation which bound the most biglycan were used to coat titanium surfaces. Bare titanium, titanium coated with collagen II fibrils and titanium coated with collagen II fibrils containing biglycan were compared. It was found that different collagen II preparations showed different affinities for CS and biglycan. In four of the five preparations tested, biglycan reduced fibril diameter, however the ability of a preparation to bind more biglycan did not appear to lead to a greater reduction in fibril diameter. Fibrils containing biglycan promoted the formation of focal adhesions by rO and significantly enhanced the proliferation of hO but not of rO or 7F2 cells. These results should encourage further investigation of biglycan as a component of collagen-based scaffolds and/or coatings.

Changes consequent to maxillary molar distalization with the bone-anchored pendulum appliance

PubMed Central

Cambiano, Aldo Otazú; Janson, Guilherme; Fuziy, Acácio; Garib, Daniela Gamba; Lorenzoni, Diego Coelho

2017-01-01

OBJECTIVES: This retrospective study aimed to evaluate the dentoalveolar, skeletal, and soft tissue effects obtained with bone-anchored pendulum appliance in patients with Class II malocclusion. MATERIALS AND METHODS: A total of 18 patients (4 male, 14 female) at a mean pretreatment age of 14.0 years (+1.08) were enrolled in this study. All patients were treated with the bone-anchored pendulum appliance for an average duration of 4.8 months. Only the active distalization period was evaluated with predistalization and postdistalization lateral cephalograms. Skeletal, dentoalveolar, and soft tissue variables were obtained. Based on these variables, the treatment effects were evaluated with dependent t-test. RESULTS: Correction of Class II molar relationship resulted from distal movement of 3.45 mm and tipping of 11.24° of the first maxillary molars. The premolars were distalized accompanying the molars. CONCLUSIONS: The bone-anchored pendulum appliance proved to be an effective method for distalization of maxillary molars in cases that require maximum anchorage, avoiding reciprocal mesial movement of premolars and incisors. PMID:29119095

Resistance Training in Type II Diabetes Mellitus: Impact on Areas of Metabolic Dysfunction in Skeletal Muscle and Potential Impact on Bone

PubMed Central

Wood, Richard J.; O'Neill, Elizabeth C.

2012-01-01

The prevalence of Type II Diabetes mellitus (T2DM) is increasing rapidly and will continue to be a major healthcare expenditure burden. As such, identification of effective lifestyle treatments is paramount. Skeletal muscle and bone display metabolic and functional disruption in T2DM. Skeletal muscle in T2DM is characterized by insulin resistance, impaired glycogen synthesis, impairments in mitochondria, and lipid accumulation. Bone quality in T2DM is decreased, potentially due to the effects of advanced glycation endproducts on collagen, impaired osteoblast activity, and lipid accumulation. Although exercise is widely recognized as an important component of treatment for T2DM, the focus has largely been on aerobic exercise. Emerging research suggests that resistance training (strength training) may impose potent and unique benefits in T2DM. The purpose of this review is to examine the role of resistance training in treating the dysfunction in skeletal muscle and the potential role for resistance training in treating the associated dysfunction in bone. PMID:22474580

The roles of vascular endothelial growth factor in bone repair and regeneration

PubMed Central

Hu, Kai; Olsen, Bjorn R.

2016-01-01

Vascular endothelial growth factor-A (VEGF) is one of the most important growth factors for regulation of vascular development and angiogenesis. Since bone is a highly vascularized organ and angiogenesis plays an important role in osteogenesis, VEGF also influences skeletal development and postnatal bone repair. Compromised bone repair and regeneration in many patients can be attributed to impaired blood supply; thus, modulation of VEGF levels in bones represents a potential strategy for treating compromised bone repair and improving bone regeneration. This review (i) summarizes the roles of VEGF at different stages of bone repair, including the phases of inflammation, endochondral ossification, intramembranous ossification during callus formation and bone remodeling; (ii) discusses different mechanisms underlying the effects of VEGF on osteoblast function, including paracrine, autocrine and intracrine signaling during bone repair; (iii) summarizes the role of VEGF in the bone regenerative procedure, distraction osteogenesis; and (iv) reviews evidence for the effects of VEGF in the context of repair and regeneration techniques involving the use of scaffolds, skeletal stem cells and growth factors. PMID:27353702

Poor nutrition in prepubertal Japanese children at the end of World War II suppressed bone development.

PubMed

Yoshimura, Toshihiro; Tohya, Toshimitsu; Onoda, Chikashi; Okamura, Hitoshi

2005-09-16

To assess the extent to which malnutrition in childhood affects bone mineral density (BMD) decades later. BMDs were compared in healthy women (35-59 years old) who visited our hospital for annual examinations between 1992 and 1993 (group 1) and between 1999 and 2002 (group 2). The BMDs of 50- to 54-year-old women in group 1 averaged 0.86+/-0.15 g/cm2, which was significantly (p<0.001) lower than age-matched women in group 2 (1.02+/-0.16 g/cm2). At the end of World War II (1945) undernutrition was rampant throughout Japan, and there were unprecedented numbers of cases of malnutrition. BMD was lower in women who experienced those conditions while they were 5 years old in average, a time when rapid skeletal growth was beginning. Thus, nutrition in childhood is a particularly crucial determinant of lifelong bone health.

A novel coupled system of non-local integro-differential equations modelling Young's modulus evolution, nutrients' supply and consumption during bone fracture healing

NASA Astrophysics Data System (ADS)

Lu, Yanfei; Lekszycki, Tomasz

2016-10-01

During fracture healing, a series of complex coupled biological and mechanical phenomena occurs. They include: (i) growth and remodelling of bone, whose Young's modulus varies in space and time; (ii) nutrients' diffusion and consumption by living cells. In this paper, we newly propose to model these evolution phenomena. The considered features include: (i) a new constitutive equation for growth simulation involving the number of sensor cells; (ii) an improved equation for nutrient concentration accounting for the switch between Michaelis-Menten kinetics and linear consumption regime; (iii) a new constitutive equation for Young's modulus evolution accounting for its dependence on nutrient concentration and variable number of active cells. The effectiveness of the model and its predictive capability are qualitatively verified by numerical simulations (using COMSOL) describing the healing of bone in the presence of damaged tissue between fractured parts.

Transient chondrogenic phase in the intramembranous pathway during normal skeletal development.

PubMed

Nah, H D; Pacifici, M; Gerstenfeld, L C; Adams, S L; Kirsch, T

2000-03-01

Calvarial and facial bones form by intramembranous ossification, in which bone cells arise directly from mesenchyme without an intermediate cartilage anlage. However, a number of studies have reported the emergence of chondrocytes from in vitro calvarial cell or organ cultures and the expression of type II collagen, a cartilage-characteristic marker, in developing calvarial bones. Based on these findings we hypothesized that a covert chondrogenic phase may be an integral part of the normal intramembranous pathway. To test this hypothesis, we analyzed the temporal and spatial expression patterns of cartilage characteristic genes in normal membranous bones from chick embryos at various developmental stages (days 12, 15 and 19). Northern and RNAse protection analyses revealed that embryonic frontal bones expressed not only the type I collagen gene but also a subset of cartilage characteristic genes, types IIA and XI collagen and aggrecan, thus resembling a phenotype of prechondrogenic-condensing mesenchyme. The expression of cartilage-characteristic genes decreased with the progression of bone maturation. Immunohistochemical analyses of developing embryonic chick heads indicated that type II collagen and aggrecan were produced by alkaline phosphatase activity positive cells engaged in early stages of osteogenic differentiation, such as cells in preosteogenic-condensing mesenchyme, the cambium layer of periosteum, the advancing osteogenic front, and osteoid bone. Type IIB and X collagen messenger RNAs (mRNA), markers for mature chondrocytes, were also detected at low levels in calvarial bone but not until late embryonic stages (day 19), indicating that some calvarial cells may undergo overt chondrogenesis. On the basis of our findings, we propose that the normal intramembranous pathway in chicks includes a previously unrecognized transient chondrogenic phase similar to prechondrogenic mesenchyme, and that the cells in this phase retain chondrogenic potential that can be expressed in specific in vitro and in vivo microenvironments.

Role of TAF12 in the Increased VDR Activity in Paget’s Disease of Bone

DTIC Science & Technology

2014-10-01

DRIP205) and VDR interacting with the histone acetyltransferases (SRC1, CBBP etc) that control entry and activity of RNA polymerase II for TAF12...bone volume fraction (BV/TV, %), trabecular number (Tb.N, N /mm2), trabecular thickness (Tb.Th, mm), and trabecular bone spacing (Tb.Sp, mm). Cortical...mean SD ( n ¼ 4); p< 0.01, significantly different from OCLs formed with the same treatment in WT mouse cultures. (B) OCL formation by treatment of

Kidney tubular-cell secretion of osteoblast growth factor is increased by kaempferol: a scientific basis for "the kidney controlling the bone" theory of Chinese medicine.

PubMed

Long, Mian; Li, Shun-xiang; Xiao, Jiang-feng; Wang, Jian; Lozanoff, Scott; Zhang, Zhi-guang; Luft, Benjamin J; Johnson, Francis

2014-09-01

To study, at the cytological level, the basic concept of Chinese medicine that "the Kidney (Shen) controls the bone". Kaempferol was isolated form Rhizoma Drynariae (Gu Sui Bu, GSB) and at several concentrations was incubated with opossum kidney (OK) cells, osteoblasts (MC3T3 E1) and human fibroblasts (HF) at cell concentrations of 2×10(4)/mL. Opossum kidney cell-conditioned culture media with kaempferol at 70 nmol/L (70kaeOKM) and without kaempferol (0OKM) were used to stimulate MC3T3 E1 and HF proliferation. The bone morphological protein receptors I and II (BMPR I and II) in OK cells were identified by immune-fluorescence staining and Western blot analysis. Kaempferol was found to increase OK cell growth (P<0.05), but alone did not promote MC3T3 E1 or HF cell proliferation. However, although OKM by itself increased MC3T3 E1 growth by 198% (P<0.01), the 70kaeOKM further increased the growth of these cells by an additional 127% (P<0.01). It indicates that the kidney cell generates a previously unknown osteoblast growth factor (OGF) and kaempferol increases kidney cell secretion of OGF. Neither of these media had any significant effect on HF growth. Kaempferol also was found to increase the level of the BMPR II in OK cells. This lends strong support to the original idea that the Kidney has a significant influence over bone-formation, as suggested by some long-standing Chinese medical beliefs, kaempferol may also serve to stimulate kidney repair and indirectly stimulate bone formation.

Clinical Forms of Canine Visceral Leishmaniasis in Naturally Leishmania infantum–Infected Dogs and Related Myelogram and Hemogram Changes

PubMed Central

Roatt, Bruno Mendes; Aguiar-Soares, Rodrigo Dian de Oliveira; Reis, Levi Eduardo Soares; Carvalho, Maria das Graças; Carneiro, Cláudia Martins; Giunchetti, Rodolfo Cordeiro; Bouillet, Leoneide Erica Maduro; Lemos, Denise Silveira; Coura-Vital, Wendel; Reis, Alexandre Barbosa

2013-01-01

Hematological analysis has limited applications for disease diagnosis in Leishmania infantum–infected dogs, but it can be very important in evaluating the clinical forms of the disease and in understanding the evolution of canine visceral leishmaniasis (CVL) pathogenesis. Recently, we demonstrated that alterations in leucopoiesis and erythropoiesis are related to clinical status and bone marrow parasite density in dogs naturally infected by L. infantum. To further characterize these alterations, we evaluated the association between the hematological parameters in bone marrow and peripheral blood alterations in groups of L. infantum–infected dogs: asymptomatic I (AD-I: serum negative/PCR+), asymptomatic II (AD-II: serum positive), oligosymptomatic (OD), and symptomatic (SD). Results were compared with those from noninfected dogs (NID). The SD group was found to present a decrease in erythropoietic lineage with concomitant reductions in erythrocytes, hemoglobin, and hematocrit parameters, resulting in anemia. The SD group also had increased neutrophils and precursors and decreased band eosinophils and eosinophils, leading to peripheral blood leucopenia. In the AD-II group, lymphocytosis occurred in both the peripheral blood and the bone marrow compartments. The SD group exhibited lymphocytosis in the bone marrow, with lymphopenia in the peripheral blood. In contrast, the AD-I group, showed no significant changes suggestive of CVL, presenting normal counts in bone marrow and peripheral blood. Our results showed for the first time that important changes in hematopoiesis and hematological parameters occur during ongoing CVL in naturally infected dogs, mainly in symptomatic disease. Taken together, our results based on myelogram and hemogram parameters enable better understanding of the pathogenesis of the anemia, lymphocytosis, and lymphopenia, as well as the leucopenia (eosinopenia and monocytopenia), that contribute to CVL prognosis. PMID:24376612

New Horizons in Osteoporosis

PubMed Central

Rachner, Tilman D.; Khosla, Sundeep; Hofbauer, Lorenz C.

2013-01-01

Summary Osteoporosis is a common disease characterised by a systemic impairment of bone mass and microarchitecture that results in fragility fractures. With an ageing population, the medical and socioeconomic impact of osteoporosis in general and postmenopausal osteoporosis in particular, will increase further. A detailed knowledge of bone biology with molecular insights into the communication between bone-forming osteoblasts and bone-resorbing osteoclasts and the orchestrating signalling network has led to the identification of novel therapeutic targets. Based on this, therapeutic strategies have been developed aimed at (I) inhibiting excessive bone resorption and by (II) increasing bone formation. The most promising novel treatments include denosumab, a monoclonal antibody against receptor activator of NF-κB ligand, a key osteoclast cytokine, odanacatib, a specific inhibitor of the osteoclast protease cathepsin K, and antibodies against the proteins sclerostin and dickkopf-1, two endogenous inhibitors of bone formation. This review provides an overview on these novel therapies and explains their underlying physiology. PMID:21450337

Osteoporosis and its association with non-gonadal hormones involved in hypertension, adiposity and hyperglycaemia.

PubMed

Poudyal, Hemant; Brown, Lindsay

2013-12-01

Osteoporosis is a high-prevalence disease, particularly in developed countries, and results in high costs both to the individual and to society through associated fragility fractures. There is an urgent need for identification of novel drug targets and development of new anti-osteoporotic agents. Between 30 and 80% of osteoporotic fractures cannot be prevented despite current treatments achieving relative fracture risk reduction of up to 20%, 50%, and 70% for non-vertebral, hip and spine fractures, respectively. Traditionally, the decline in gonadal hormones has been studied as the sole hormonal determinant for the loss of bone mineral density in osteoporosis. However, recent studies have identified receptors for numerous non-gonadal hormones such as PTH, angiotensin II, leptin, adiponectin, insulin and insulin-like growth factor-1 on the osteoblast lineage cells that directly regulate bone turnover. These hormones are also involved in the pathogenesis of metabolic syndrome risk factors, particularly hypertension, type-II diabetes and obesity. By activating their respective receptors on osteoblastic lineage cells, these hormones appear to act through a common mechanism by down-regulating receptors for activation of nuclear factor kappa B ligand (RANKL) and up-regulating osteoprotegerin (OPG) with inverse responses for adiponectin. Receptors for amylin, gastric inhibitory polypeptide and ghrelin and have also been identified on the osteoblast lineage cells although the roles of these receptors in bone turnover are controversial or poorly studied. Moreover, bone turnover may be independently regulated by modulation of osteoclast-osteoblast function and bone marrow adiposity. Leptin appears to be the only hormone that is a known regulator of both bone mineralisation and bone adiposity.

Combined application of latissimus dorsi myocutaneous flap and iliac bone flap in the treatment of chronic osteomyelitis of the lower extremity.

PubMed

Ju, Jihui; Li, Lei; Zhou, Rong; Hou, Ruixing

2018-05-18

To evaluate the clinical efficacy and safety of latissimus dorsi myocutaneous flap (stage I) combined with iliac bone flap (stage II) in the treatment of chronic osteomyelitis of the lower extremity. Clinical data of 18 patients undergoing latissimus dorsi myocutaneous flap in combination with iliac bone flap grafting were retrospectively analyzed. Among them, 2 patients developed chronic osteomyelitis of the lower segment of the femur, 4 were diagnosed with chronic osteomyelitis of the tibial plateau, and 12 with chronic osteomyelitis of the lower segment of the tibia. All the latissimus dorsi myocutaneous flaps survived in 18 patients. After the corresponding surgery, primary wound healing was achieved in 11 patients, and delayed wound healing was obtained in 7 cases. All wounds were completely healed with postoperative 2 months. Following the iliac bone flap grafting, primary would healing was accomplished in all cases. All dorsal window chambers survived. The bone defects were properly restored within 4-12 postoperative months. Functional training was performed after removal of the internal and external fixators. Postoperative follow-up was endured from 6 months to 10 years. All patients were satisfied with the bone healing and flap texture without the incidence of osteomyelitis and sinus tract. No contraction was observed in the grafting area of 2 patients receiving latissimus dorsi myocutaneous flap grafting. Residual linear scars were noted in the dorsal and iliac donor sites. Combined usage of stage I latissimus dorsi myocutaneous flap and stage II iliac bone flap grafting is an efficacious and safe surgical technique in clinical practice.

Assessment of copper removal from highway stormwater runoff using Apatite II(TM) and compost : laboratory and field testing.

DOT National Transportation Integrated Search

2015-03-01

-Stormwater runoff introduces heavy metals to surface waters that are harmful to aquatic organisms, : including endangered salmon. This work evaluates Apatite II, a biogenic fish bone based adsorbent, for removing metal : from stormwater. The meta...

Monomeric, porous type II collagen scaffolds promote chondrogenic differentiation of human bone marrow mesenchymal stem cells in vitro

NASA Astrophysics Data System (ADS)

Tamaddon, M.; Burrows, M.; Ferreira, S. A.; Dazzi, F.; Apperley, J. F.; Bradshaw, A.; Brand, D. D.; Czernuszka, J.; Gentleman, E.

2017-03-01

Osteoarthritis (OA) is a common cause of pain and disability and is often associated with the degeneration of articular cartilage. Lesions to the articular surface, which are thought to progress to OA, have the potential to be repaired using tissue engineering strategies; however, it remains challenging to instruct cell differentiation within a scaffold to produce tissue with appropriate structural, chemical and mechanical properties. We aimed to address this by driving progenitor cells to adopt a chondrogenic phenotype through the tailoring of scaffold composition and physical properties. Monomeric type-I and type-II collagen scaffolds, which avoid potential immunogenicity associated with fibrillar collagens, were fabricated with and without chondroitin sulfate (CS) and their ability to stimulate the chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells was assessed. Immunohistochemical analyses showed that cells produced abundant collagen type-II on type-II scaffolds and collagen type-I on type-I scaffolds. Gene expression analyses indicated that the addition of CS - which was released from scaffolds quickly - significantly upregulated expression of type II collagen, compared to type-I and pure type-II scaffolds. We conclude that collagen type-II and CS can be used to promote a more chondrogenic phenotype in the absence of growth factors, potentially providing an eventual therapy to prevent OA.

An Electrochemical DNA Biosensor for the Detection of Salmonella Using Polymeric Films and Electrochemical Labels

NASA Astrophysics Data System (ADS)

Diaz Serrano, Madeline

Waterborne and foodborne diseases are one of the principal public health problems worldwide. Microorganisms are the major agents of foodborne illness: pathogens such as Salmonella, Campylobacter jejuni and Escherichia coli, and parasites such as cryptosporidium. The most popular methods to detect Salmonella are based on culture and colony counting methods, ELISA, Gel electrophoresis and the polymerase chain reaction. Conventional detection methods are laborious and time-consuming, allowing for portions of the food to be distributed, marketed, sold and eaten before the analysis is done and the problem even detected. By these reasons, the rapid, easy and portable detection of foodborne organisms will facilitate the disease treatment. Our particular interest is to develop a nucleic acid biosensor (NAB) for the detection of pathogenic microorganisms in food and water samples. In this research, we report on the development of a NAB prototype using a polymer modified electrode surface together with sequences of different lengths for the OmpC gene from Salmonella as probes and Ferrocene-labeled target (Fc-ssDNA), Ferrocene-labeled tri(ethylene glycol) (Fc-PEG) and Ruthenium-Ferrocene (Ru-Fe) bimetallic complex as an electrochemical labels. We have optimized several PS films and anchored nucleic acid sequences with different lengths at gold and carbon surfaces. Non contact mode AFM and XPS were used to monitor each step of the NAB preparation, from polymer modification to oligos hybridization (conventional design). The hybridization reaction was followed electrochemically using a Fc-ssDNA and Fc-PEG in solution taking advantage of the morphological changes generated upon hybridization. We observed a small current at the potential for the Fe oxidation without signal amplification at +296 mV vs. Ag/AgCl for the Fc-ssDNA strategy and a small current at +524 mV for the Fc-PEG strategy. The immobilization, hybridization and signal amplification of Biotin- OmpC Salmonella genes generated by E.Z. Vega were obtained on NHS-PS-NHS 10.3 KD and detected by SWV and CC using Ru-Fe bimetallic complex as a redox label and GOx/glucose in PBS buffer. Calibration curves of biotin-OmpC probe hybridization were performed by CC, a catalytic charge was observed due to the presence of Ru-Fe bimetallic complex, GOx-A and glucose. The lowest target sequence detectable concentration was 0.41 microM.

Preparation and Characterization of Activated Cow Bone Powder for the Adsorption of Cadmium from Palm Oil Mill Effluent

NASA Astrophysics Data System (ADS)

AbdulRahman, A.; Latiff, A. A. A.; Daud, Z.; Ridzuan, M. B.; D, N. F. M.; Jagaba, A. H.

2016-07-01

Several studies have been conducted on the removal of heavy metals from palm oil mill effluent. In this study, cow bones were developed as an adsorbent for the removal of cadmium II from POME. A batch experiment was conducted to investigate the effectiveness of the prepared activated cow bone powder for the sorption of cadmium II from raw POME. The experiment was carried out under fixed conditions using 100mg/L raw POME combined with different adsorbent dosage of CBP of 184.471 Ra(nm) surface roughness. The equilibrium adsorption capacity of the hydrophobic CBP of average contact angle 890 was determined from the relationship between the initial and equilibrium liquid phase concentrations of POME. The optimum adsorption of cadmium II on CBP was at 10g adsorbent dosage for sample 1 and 2 at 97.8% and 96.93% respectively. The least uptake was at 30g adsorbent weight for both samples at average of 95.1% for both samples. The effective removal of cadmium ion showed that CBP has a great potential for the treatment of heavy metal in POME.

Single-screw Fixation of Adolescent Salter-II Proximal Humeral Fractures: Biomechanical Analysis of the "One Pass Door Lock" Technique.

PubMed

Miller, Mark Carl; Redman, Christopher N; Mistovich, R Justin; Muriuki, Muturi; Sangimino, Mark J

2017-09-01

Pin fixation of Salter-II proximal humeral fractures in adolescents approaching skeletal maturity has potential complications that can be avoided with single-screw fixation. However, the strength of screw fixation relative to parallel and diverging pin fixation is unknown. To compare the biomechanical fixation strength between these fixation modalities, we used synthetic composite humeri, and then compared these results in composite bone with cadaveric humeri specimens. Parallel pinning, divergent pinning, and single-screw fixation repairs were performed on synthetic composite humeri with simulated fractures. Six specimens of each type were tested in axial loading and other 6 were tested in torsion. Five pair of cadaveric humeri were tested with diverging pins and single screws for comparison. Single-screw fixation was statistically stronger than pin fixation in axial and torsional loading in both composite and actual bone. There was no statistical difference between composite and cadaveric bone specimens. Single-screw fixation can offer greater stability to adolescent Salter-II fractures than traditional pinning. Single-screw fixation should be considered as a viable alternative to percutaneous pin fixation in transitional patients with little expected remaining growth.

Role of clinician's experience and implant design on implant stability. An ex vivo study in artificial soft bones.

PubMed

Romanos, Georgios E; Basha-Hijazi, Abdulaziz; Gupta, Bhumija; Ren, Yan-Fang; Malmstrom, Hans

2014-04-01

Clinical experience in implant placement is important in order to prevent implant failures. However, the implant design affects the primary implant stability (PS) especially in poor quality bones. Therefore, the aim of this study was to compare the effect of clinician surgical experience on PS, when placing different type of implant designs. A total of 180 implants (90 parallel walled-P and 90 tapered-T) were placed in freshly slaughtered cow ribs. Bone quality was evaluated by two examiners during surgery and considered as 'type IV' bone. Implants (ø 5 mm, length: 15 mm, Osseotite, BIOMET 3i, Palm Beach Gardens, FL, USA) were placed by three different clinicians (master/I, good/II, non-experienced/III, under direct supervision of a manufacturer representative; 30 implants/group). An independent observer assessed the accuracy of placement by resonance frequency analysis (RFA) with implant stability quotient (ISQ) values. Two-way analysis of variance (ANOVA) and Tukey's post hoc test were used to detect the surgical experience of the clinicians and their interaction and effects of implant design on the PS. All implants were mechanically stable. The mean ISQ values were: 49.57(± 18.49) for the P-implants and 67.07(± 8.79) for the T-implants. The two-way ANOVA showed significant effects of implant design (p < .0001), clinician (p < .0001), and their interaction (p < .0001). The Tukey's multiple comparison test showed significant differences in RFA for the clinician group I/II (p = .015) and highly significant (p < .0001) between I/III and II/III. The P-implants presented (for I, II, and III) mean ISQ values 31.25/49.18/68.17 and the T-implants showed higher ISQ values, 70.15/62.08/68.98, respectively. Clinicians I and II did not show extreme differences for T-implants (p = .016). In contrast, clinician III achieved high ISQ values using P- and T-implants following the exact surgical protocol based on the manufacturer guidelines. T-implants provided high stability for experienced clinicians compared with P-implants. T-implants achieved greater PS than the P-implants. All clinicians consistently achieved PS; however, experienced clinicians achieved higher ISQ values with T-implants in poor quality bone. © 2012 Wiley Periodicals, Inc.

ACTN3 R577X Genotypes Associate with Class II and Deep Bite Malocclusions

PubMed Central

Zebrick, Brian; Teeramongkolgul, Teesit; Nicot, Romain; Horton, Michael J.; Raoul, Gwenael; Ferri, Joel; Vieira, Alexandre R.; Sciote, James J.

2014-01-01

Introduction α-actinins are myofibril anchor proteins which influence contractile properties of skeletal muscle. ACTN2 is expressed in slow type I and fast type II fibers whereas ACTN3 is expressed only in fast fibers. ACTN3 homozygosity for the 577X stop codon (i.e. changing 577RR to 577XX - the R577X polymorphism) results in the absence of α-actinin-3 in about 18% of Europeans, diminished fast contractile ability, enhanced endurance performance and reduced bone mass or bone mineral density. We have examined ACTN3 expression and genetic variation in masseter muscle of orthognathic surgery patients to determine genotype associations with malocclusion. Methods Clinical information, masseter muscle biopsies and saliva samples were obtained from 60 subjects. Genotyping for ACTN3 SNPs, RT-PCR quantitation of muscle gene message and muscle morphometric fiber type properties were compared to determine statistical differences between genotype and phenotype. Results Muscle mRNA expression level was significantly different for ACTN3 SNP genotypes (p<0.01). The frequency of ACTN3 genotypes was significantly different for sagittal and vertical classifications of malocclusion with the clearest association being elevated 577XX genotype in skeletal class II malocclusion (p = 0.003). This genotype also resulted in significantly smaller diameter of fast type II fibers in masseter muscle (p = 0.002). Conclusion ACTN3 577XX is overrepresented in skeletal class II malocclusion, suggesting a biologic influence during bone growth. ACTN3 577XX is underrepresented in deep bite malocclusion, suggesting muscle differences contribute to variations in vertical facial dimensions. PMID:25439211

Evaluation of Anterior Vertebral Interbody Fusion Using Osteogenic Mesenchymal Stem Cells Transplanted in Collagen Sponge.

PubMed

Yang, Wencheng; Dong, Youhai; Hong, Yang; Guang, Qian; Chen, Xujun

2016-05-01

The study used a rabbit model to achieve anterior vertebral interbody fusion using osteogenic mesenchymal stem cells (OMSCs) transplanted in collagen sponge. We investigated the effectiveness of graft material for anterior vertebral interbody fusion using a rabbit model by examining the OMSCs transplanted in collagen sponge. Anterior vertebral interbody fusion is commonly performed. Although autogenous bone graft remains the gold-standard fusion material, it requires a separate surgical procedure and is associated with significant short-term and long-term morbidity. Recently, mesenchymal stem cells from bone marrow have been studied in various fields, including posterolateral spinal fusion. Thus, we hypothesized that cultured OMSCs transplanted in porous collagen sponge could be used successfully even in anterior vertebral interbody fusion. Forty mature male White Zealand rabbits (weight, 3.5-4.5 kg) were randomly allocated to receive one of the following graft materials: porous collagen sponge plus cultured OMSCs (group I); porous collagen sponge alone (group II); autogenous bone graft (group III); and nothing (group IV). All animals underwent anterior vertebral interbody fusion at the L4/L5 level. The lumbar spine was harvested en bloc, and the new bone formation and spinal fusion was evaluated using radiographic analysis, microcomputed tomography, manual palpation test, and histologic examination at 8 and 12 weeks after surgery. New bone formation and bony fusion was evident as early as 8 weeks in groups I and III. And there was no statistically significant difference between 8 and 12 weeks. At both time points, by microcomputed tomography and histologic analysis, new bone formation was observed in both groups I and III, fibrous tissue was observed and there was no new bone in both groups II and IV; by manual palpation test, bony fusion was observed in 40% (4/10) of rabbits in group I, 70% (7/10) of rabbits in group III, and 0% (0/10) of rabbits in both groups II and IV. These findings suggest that mesenchymal stem cells that have been cultured with osteogenic differentiation medium and loaded with collagen sponge could induce bone formation and anterior vertebral interbody fusion. And the rabbit model we developed will be useful in evaluating the effects of graft materials for anterior vertebral interbody fusion. Further study is needed to determine the most appropriate carrier for OMSCs and the feasibility in the clinical setting.

Isolation of an inhibitory insulin-like growth factor (IGF) binding protein from bone cell-conditioned medium: A potential local regulator of IGF action

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

Mohan, S.; Bautista, C.M.; Wergedal, J.

1989-11-01

Inhibitory insulin-like growth factor binding protein (In-IGF-BP) has been purified to homogeneity from medium conditioned by TE89 human osteosarcoma cells by two different methods using Sephadex G-100 gel filtration, FPLC Mono Q ion-exchange, HPLC C{sub 4} reverse-phase, HPLC CN reverse-phase and affinity chromatographies. In-IGF-BP thus purified appeared to be homogeneous and unique by the following criteria. (i) N-terminal sequence analysis yielded a unique sequence (Asp-Glu-Ala-Ile-His-Cys-Pro-Pro-Glu-Ser-Glu-Ala-Lys-Leu-Ala). (ii) Amino acid composition of In-IGF-BP revealed marked differences with the amino acid compositions of other known PBs. (iii) In-IGF-BP exhibited a single band with molecular mass of 25 kDa under reducing conditions on sodiummore » dodecyl sulfate/polyacrylamide gels. IGF-I and IGF-II but not insulin displaced the binding of {sup 125}I-labeled IGF-I or {sup 125}I-labeled IGF-II binding to In-IGF-BP. In-IGF-BP inhibited basal, IGF-stimulated bone cell proliferation and serum-stimulated bone cell proliferation. Forskolin increases synthesis of In-IGF-BP in TE85 human osteosarcoma cells in a dose-dependent manner. Based on these findings, the authors conclude that In-IGF-BP is a protein that has a unique sequence and significant biological actions on bone cells.« less

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

PubMed

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

2017-04-01

The components of renin-angiotensin system (RAS) are expressed in the kidney and bone. Kidney disease and bone injury are common complications associated with diabetes. This study aimed to investigate the effects of an angiotensin-converting enzyme inhibitor, captopril, on the kidney and bone of db/db mice. The db/db mice were orally administered by gavage with captopril for 8weeks with db/+ mice as the non-diabetic control. Serum and urine biochemistries were determined by standard colorimetric methods or ELISA. Histological measurements were performed on the kidney by periodic acid-schiff staining and on the tibial proximal metaphysis by safranin O and masson-trichrome staining. Trabecular bone mass and bone quality were analyzed by microcomputed tomography. Quantitative polymerase chain reaction and immunoblotting were applied for molecular analysis on mRNA and protein expression. Captopril significantly improved albuminuria and glomerulosclerosis in db/db mice, and these effects might be attributed to the down-regulation of angiotensin II expression and the expression of its down-stream profibrotic factors in the kidney, like connective tissue growth factor and vascular endothelial growth factor. Urinary excretion of calcium and phosphorus markedly increased in db/db mice in response to captopril. Treatment with captopril induced a decrease in bone mineral density and deterioration of trabecular bone at proximal metaphysis of tibia in db/db mice, as shown in the histological and reconstructed 3-dimensional images. Even though captopril effectively reversed the diabetes-induced changes in calcium-binding protein 28-k and vitamin D receptor expression in the kidney as well as the expression of RAS components and bradykinin receptor-2 in bone tissue, treatment with captopril increased the osteoclast-covered bone surface, reduced the osteoblast-covered bone surface, down-regulated the expression of type 1 collagen and transcription factor runt-related transcription factor 2 (markers for osteoblastic functions), and up-regulated the expression of carbonic anhydrase II (marker for bone resorption). Captopril exerted therapeutic effects on renal injuries associated with type 2 diabetes but worsened the deteriorations of trabecular bone in db/db mice; the latter of which was at least in part due to the stimulation of osteoclastogenesis and the suppression of osteogenesis by captopril. Copyright © 2017 Elsevier Inc. All rights reserved.

Vascularised endosteal bone tissue in armoured sauropod dinosaurs.

PubMed

Chinsamy, Anusuya; Cerda, Ignacio; Powell, Jaime

2016-04-26

The presence of well-vascularised, endosteal bone in the medullary region of long bones of nonavian dinosaurs has been invoked as being homologous to medullary bone, a specialised bone tissue formed during ovulation in birds. However, similar bone tissues can result as a pathological response in modern birds and in nonavian dinosaurs, and has also been reported in an immature nonavian dinosaur. Here we report on the occurrence of well-vascularised endosteally formed bone tissue in three skeletal elements of armoured titanosaur sauropods from the Upper Cretaceous of Argentina: i) within the medullary cavity of a metatarsal, ii) inside a pneumatic cavity of a posterior caudal vertebra, iii) in intra-trabecular spaces in an osteoderm. We show that considering the criteria of location, origin (or development), and histology, these endosteally derived tissues in the saltasaurine titanosaurs could be described as either medullary bone or pathological bone. Furthermore, we show that similar endosteally formed well-vascularised bone tissue is fairly widely distributed among nondinosaurian Archosauriformes, and are not restricted to long bones, but can occur in the axial, and dermal skeleton. We propose that independent evidence is required to verify whether vascularised endosteal bone tissues in extinct archosaurs are pathological or reproductive in nature.

Vascularised endosteal bone tissue in armoured sauropod dinosaurs

PubMed Central

Chinsamy, Anusuya; Cerda, Ignacio; Powell, Jaime

2016-01-01

The presence of well-vascularised, endosteal bone in the medullary region of long bones of nonavian dinosaurs has been invoked as being homologous to medullary bone, a specialised bone tissue formed during ovulation in birds. However, similar bone tissues can result as a pathological response in modern birds and in nonavian dinosaurs, and has also been reported in an immature nonavian dinosaur. Here we report on the occurrence of well-vascularised endosteally formed bone tissue in three skeletal elements of armoured titanosaur sauropods from the Upper Cretaceous of Argentina: i) within the medullary cavity of a metatarsal, ii) inside a pneumatic cavity of a posterior caudal vertebra, iii) in intra-trabecular spaces in an osteoderm. We show that considering the criteria of location, origin (or development), and histology, these endosteally derived tissues in the saltasaurine titanosaurs could be described as either medullary bone or pathological bone. Furthermore, we show that similar endosteally formed well-vascularised bone tissue is fairly widely distributed among nondinosaurian Archosauriformes, and are not restricted to long bones, but can occur in the axial, and dermal skeleton. We propose that independent evidence is required to verify whether vascularised endosteal bone tissues in extinct archosaurs are pathological or reproductive in nature. PMID:27112710

Morphology of bone particles after harvesting with 4 different devices.

PubMed

Papadimitriou, Dimitrios E V; Schmidt, Erich C; Caton, Jack G; Romanos, Georgios E

2013-04-01

Autogenous bone is routinely used for regeneration of osseous defects around teeth and implants, and different instruments are available for bone harvesting. The purpose of this study was to describe the morphology of bone particles after harvesting with 4 different instruments. Bone particles were harvested from fresh cow ribs with 2 different types of back action chisels, a safescraper and a sonic device. The samples were examined morphologically using light microscopy and scanning electron microscopy. The bone particles after the back action chisel I had an appearance similar to "pencil shavings." With the back action chisel II, they were like thin paper with an "accordion bellows" appearance. After removal with the safescraper, they had an irregular shape (with an irregular surface) resembling "crushed stone." Finally, the appearance of the bone particles obtained with the sonic device was homogenous, condensed and continuous, and had a "seaweed" appearance. Harvesting of bone particles with 4 different devices produce distinctly difference sizes and shapes, which may influence the results of grafting procedures.

Peri-implant soft tissue and marginal bone adaptation on implant with non-matching healing abutments: micro-CT analysis.

PubMed

Finelle, Gary; Papadimitriou, Dimitrios E V; Souza, André B; Katebi, Negin; Gallucci, German O; Araújo, Mauricio G

2015-04-01

To assess (i) the outcome of changing the horizontal-offset dimension on the peri-implant soft tissues and the crestal bone and (ii) the effect of different healing abutments (flared vs. straight) on the marginal peri-implant soft tissues and crestal bone. Two-piece dental implants diameters of 3.5 and 4.5 mm were placed at least 1 mm subcrestal in five beagle dogs. Three different investigational groups: (i) 3.5-mm-diameter implant with narrow healing abutment (3.5N), (ii) 4.5-mm-diameter implant with narrow healing abutment (4.5N), and (iii) 3.5-mm-diameter implant with wide healing abutment (3.5W), were assessed. After 4 months of healing, the vertical distance from the marginal crestal bone (MB) to the implant shoulder (IS); the vertical distance from the IS to the first bone-to-implant contact; and the horizontal distance of bone ingrowth on the implant platform were measured with a high-resolution micro-CT (Xradia MicroXCT-200 system). Implants with a narrow healing caps showed an interproximal MB located between 0 and 1 mm above the implant shoulder, while the 3.5W group exhibits a mean value -0.50 mm. As all implants in group 3.5N presented a fBIC located at the level of the IS. For the 4.5N group, the mean fBIC-IS distance was -0.52 mm apically to the IS. For the 3.5WC group, the mean fBIC-IS distance was -1.42 mm. Horizontal bone apposition was only observed for the 3.5N group and the 4.5N group. The dimension of the horizontal offset would play a minimal role in reducing bone remodeling, whereas the configuration of the transmucosal component would directly influence marginal bone remodeling. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Alteration of the bone tissue material properties in type 1 diabetes mellitus: A Fourier transform infrared microspectroscopy study.

PubMed

Mieczkowska, Aleksandra; Mansur, Sity Aishah; Irwin, Nigel; Flatt, Peter R; Chappard, Daniel; Mabilleau, Guillaume

2015-07-01

Type 1 diabetes mellitus (T1DM) is a severe disorder characterized by hyperglycemia and hypoinsulinemia. A higher occurrence of bone fractures has been reported in T1DM, and although bone mineral density is reduced in this disorder, it is also thought that bone quality may be altered in this chronic pathology. Vibrational microscopies such as Fourier transform infrared microspectroscopy (FTIRM) represent an interesting approach to study bone quality as they allow investigation of the collagen and mineral compartment of the extracellular matrix in a specific bone location. However, as spectral feature arising from the mineral may overlap with those of the organic component, the demineralization of bone sections should be performed for a full investigation of the organic matrix. The aims of the present study were to (i) develop a new approach, based on the demineralization of thin bone tissue section to allow a better characterization of the bone organic component by FTIRM, (ii) to validate collagen glycation and collagen integrity in bone tissue and (iii) to better understand what alterations of tissue material properties in newly forming bone occur in T1DM. The streptozotocin-injected mouse (150 mg/kg body weight, injected at 8 weeks old) was used as T1DM model. Animals were randomly allocated to control (n = 8) or diabetic (n = 10) groups and were sacrificed 4 weeks post-STZ injection. Bones were collected at necropsy, embedded in polymethylmethacrylate and sectioned prior to examination by FTIRM. FTIRM collagen parameters were collagen maturity (area ratio between 1660 and 1690 cm(-1) subbands), collagen glycation (area ratio between the 1032 cm(-1) subband and amide I) and collagen integrity (area ratio between the 1338 cm(-1) subband and amide II). No significant differences in the mineral compartment of the bone matrix could be observed between controls and STZ-injected animals. On the other hand, as compared with controls, STZ-injected animals presented with significant higher value for collagen maturity (17%, p = 0.0048) and collagen glycation (99%, p = 0.0121), while collagen integrity was significantly lower by 170% (p = 0.0121). This study demonstrated the profound effect of early T1DM on the organic compartment of the bone matrix in newly forming bone. Further studies in humans are required to ascertain whether T1DM also lead to similar effect on the quality of the bone matrix. Copyright © 2015 Elsevier Inc. All rights reserved.

Ang II-AT2R increases mesenchymal stem cell migration by signaling through the FAK and RhoA/Cdc42 pathways in vitro.

PubMed

Xu, Xiu-Ping; He, Hong-Li; Hu, Shu-Ling; Han, Ji-Bin; Huang, Li-Li; Xu, Jing-Yuan; Xie, Jian-Feng; Liu, Ai-Ran; Yang, Yi; Qiu, Hai-Bo

2017-07-12

Mesenchymal stem cells (MSCs) migrate via the bloodstream to sites of injury and are possibly attracted by inflammatory factors. As a proinflammatory mediator, angiotensin II (Ang II) reportedly enhances the migration of various cell types by signaling via the Ang II receptor in vitro. However, few studies have focused on the effects of Ang II on MSC migration and the underlying mechanisms. Human bone marrow MSCs migration was measured using wound healing and Boyden chamber migration assays after treatments with different concentrations of Ang II, an AT1R antagonist (Losartan), and/or an AT2R antagonist (PD-123319). To exclude the effect of proliferation on MSC migration, we measured MSC proliferation after stimulation with the same concentration of Ang II. Additionally, we employed the focal adhesion kinase (FAK) inhibitor PF-573228, RhoA inhibitor C3 transferase, Rac1 inhibitor NSC23766, or Cdc42 inhibitor ML141 to investigate the role of cell adhesion proteins and the Rho-GTPase protein family (RhoA, Rac1, and Cdc42) in Ang II-mediated MSC migration. Cell adhesion proteins (FAK, Talin, and Vinculin) were detected by western blot analysis. The Rho-GTPase family protein activities were assessed by G-LISA and F-actin levels, which reflect actin cytoskeletal organization, were detected by using immunofluorescence. Human bone marrow MSCs constitutively expressed AT1R and AT2R. Additionally, Ang II increased MSC migration in an AT2R-dependent manner. Notably, Ang II-enhanced migration was not mediated by Ang II-mediated cell proliferation. Interestingly, Ang II-enhanced migration was mediated by FAK activation, which was critical for the formation of focal contacts, as evidenced by increased Talin and Vinculin expression. Moreover, RhoA and Cdc42 were activated by FAK to increase cytoskeletal organization, thus promoting cell contraction. Furthermore, FAK, Talin, and Vinculin activation and F-actin reorganization in response to Ang II were prevented by PD-123319 but not Losartan, indicating that FAK activation and F-actin reorganization were downstream of AT2R. These data indicate that Ang II-AT2R regulates human bone marrow MSC migration by signaling through the FAK and RhoA/Cdc42 pathways. This study provides insights into the mechanisms by which MSCs home to injury sites and will enable the rational design of targeted therapies to improve MSC engraftment.

Effects of losartan treatment on the physicochemical properties of diabetic rat bone.

PubMed

Donmez, Baris Ozgur; Unal, Mustafa; Ozdemir, Semir; Ozturk, Nihal; Oguz, Nurettin; Akkus, Ozan

2017-03-01

Inhibitors of the renin-angiotensin system used to treat several diseases have also been shown to be effective on bone tissue, suggesting that angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may reduce fracture risk. The present study investigated the effects of losartan on the physicochemical and biomechanical properties of diabetic rat bone. Losartan (5 mg/kg/day) was administered via oral gavage for 12 weeks. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry. Whole femurs were tested under tension to evaluate the biomechanical properties of bone. The physicochemical properties of bone were analyzed by Fourier transform infrared spectroscopy. Although losartan did not recover decreases in the BMD of diabetic bone, it recovered the physicochemical (mineral and collagen matrix) properties of diabetic rat bone. Furthermore, losartan also recovered ultimate tensile strength of diabetic rat femurs. Losartan, an angiotensin II type 1 receptor blocker, has a therapeutic effect on the physicochemical properties of diabetic bone resulting in improvement of bone strength at the material level. Therefore, specific inhibition of this pathway at the receptor level shows potential as a therapeutic target for diabetic patients suffering from bone diseases such as osteopenia.

Development of an injectable pseudo-bone thermo-gel for application in small bone fractures.

PubMed

Kondiah, Pariksha J; Choonara, Yahya E; Kondiah, Pierre P D; Kumar, Pradeep; Marimuthu, Thashree; du Toit, Lisa C; Pillay, Viness

2017-03-30

A pseudo-bone thermo-gel was synthesized and evaluated for its physicochemical, mechanical and rheological properties, with its application to treat small bone fractures. The pseudo-bone thermo-gel was proven to have thermo-responsive properties, behaving as a solution in temperatures below 25°C, and forming a gelling technology when maintained at physiological conditions. Poly propylene fumerate (PPF), Pluronic F127 and PEG-PCL-PEG were strategically blended, obtaining a thermo-responsive delivery system, to mimic the mechanical properties of bone with sufficient matrix hardness and resilience. A Biopharmaceutics Classification System (BCS) class II drug, simvastatin, was loaded in the pseudo-bone thermo-gel, selected for its bone healing properties. In vitro release analysis was undertaken on a series of experimental formulations, with the ideal formulations obtaining its maximum controlled drug release profile up to 14days. Ex vivo studies were undertaken on an induced 4mm diameter butterfly-fractured osteoporotic human clavicle bone samples. X-ray, ultrasound as well as textural analysis, undertaken on the fractured bones before and after treatment displayed significant bone filling, matrix hardening and matrix resilience properties. These characteristics of the pseudo-bone thermo-gel thus proved significant potential for application in small bone fractures. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of Short Term Immunotoxicological Assays for Prediction of Chronic Toxicological Responses Induced by Environmental Chemicals

DTIC Science & Technology

1986-11-25

Time 16 El E 4. IUdR Incorporation into Sp*,een Cells as .Function of Preincubationr :ime.II....... ... ...... ........ I...... I........ I...trichloroethylene B) Bone marrow parameters 1) Bone marrow cell number 3) Bone marrow stem cell number (CFU-GM) Y . ,.= z , 0 .2 Cc-C 02 @13 .~ LL 0 CL uj 0...lipopolysac- • .4 -C.- * 50 Figure 21 S pleen Cell Number In Cultures 8- Exposed to S3. Mixes .............. 6 2. 0 60 180 Exposure Time (Minutes) El No S9

Retrospective Audit: Does Prior Assessment by Oral and Maxillofacial Surgeons Reduce the Risk of Osteonecrosis of The Jaw in Patients Receiving Bone-Targeted Therapies for Metastatic Cancers to the Skeleton?--Part II.

PubMed

Turner, Bruce; Ali, Sacha; Pati, Jhumur; Nargund, Vinod; Ali, Enamul; Cheng, Leo; Wells, Paula

2016-01-01

Men who receive bone-targeted therapy for metastatic prostate cancer are at increased risk of osteonecrosis of the jaw (ONJ). Development of ONJ has been associated with the administration of bone-targeted therapies in association with other risk factors. ONJ can be distressing for a patient because it can cause pain, risk of jaw fracture, body image disturbance, difficultly eating, and difficulty maintaining good oral hygiene. The aim of this article is to report results of an audit of prior assessment by oral and maxillofacial surgeons (OMFS) before initiation of bone-targeted therapies and whether it may reduce the risk of ONJ in patients receiving bone-targeted therapies for advanced cancers.

Studies the alterations of biochemical and mineral contents in bone tissue of mus musculus due to aluminum toxicity and the protective action of desferrioxamine and deferiprone by FTIR, ICP-OES, SEM and XRD techniques.

PubMed

Sivakumar, S; Khatiwada, Chandra Prasad; Sivasubramanian, J

2014-05-21

The present study has attempt to analyze the changes in the biochemical and mineral contents of aluminum intoxicated bone and determine the protective action of desferrioxamine (DFO) and deferiprone (DFP) by using Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), inductively coupled plasma optical emission spectroscopy (ICP-OES), and scanning electron microscopy (SEM) techniques for four groups of animals such as control (Group I), aluminum intoxicated (Group II), Al+DFP (Group III) and Al+DFO+DFP (Group IV) treated groups respectively. The FTIR spectra of the aluminum intoxicated bone showed significant alteration in the biochemical constituents. The bands ratio at I1400/I877 significantly decreased from control to aluminum, but enhanced it by Al+DFP to Al+DFO+DFP treated bone tissue for treatments of 16 weeks. This result suggests that DFO and DFP are the carbonate inhibitor, recovered from chronic growth of bone diseases and pathologies. The alteration of proteins profile indicated by Amide I and Amide II, where peak area values decreased from control to aluminum respectively, but enhanced by treated with DFP (p.o.) and DFO+DFP (i.p.) respectively. The XRD analysis showed a decrease in crystallinity due to aluminum toxicity. Further, the Ca, Mg, and P contents of the aluminum exposed bone were less than those of the control group, and enhanced by treatments with DFO and DFP. The concentrations of trace elements were found by ICP-OES. Therefore, present study suggests that due to aluminum toxicity severe loss of bone minerals, decrease in the biochemical constituents and changes in the surface morphology. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of LED phototherapy on bone defects grafted with MTA, bone morphogenetic proteins, and guided bone regeneration in a rodent model: a description of the bone repair by light microscopy

NASA Astrophysics Data System (ADS)

Pinheiro, Antonio Luiz B.; Aciole, Gilberth T. S.; Soares, Luiz G. P.; Correia, Neandder A.; N. dos Santos, Jean

2011-03-01

We carried out a histological analysis on surgical bone defects grafted or not with MTA, treated or not with LED, BMPs and GBR. We have used several models to assess the effects of laser on bone. Benefits of the isolated or combined use them on bone healing has been suggested. There is no previous report on their association with LED light. 90 rats were divided into 10 groups. On Groups II and I the defect were filled with the clot. On Group II, were further irradiated. On groups III-VI, defect was filled with MTA + Collagen gel (III); animals of group IV were further irradiated. On groups V and VI, the defects filled with the MTA were covered with a membrane. Animals of Group VI were further irradiated. On Groups VII and VIII a pool of BMPs was added to the MTA and was further irradiated. On groups IX and X, the MTA + BMP graft was covered with a membrane. On group X, the defect was further irradiated. LED (λ850 +/- 10nm, 150mW, A= 0.5cm2, 54s, 0.3W/cm2, 16 J/cm2) was applied at 48 h intervals during 15 days. Specimens were taken, processed, cut and stained with H&E and Sirius red and underwent histological analysis. The results showed that MTA seemed not being affected by LED light. However, its use positively affected healing around the graft. It is concluded that MTA is not affected by the LED light due to it characteristics, but beneficial results with LED usage was found.

End-threaded intramedullary positive profile screw ended self-tapping pin (Admit pin) - A cost-effective novel implant for fixing canine long bone fractures.

PubMed

Chanana, Mitin; Kumar, Adarsh; Tyagi, Som Prakash; Singla, Amit Kumar; Sharma, Arvind; Farooq, Uiase Bin

2018-02-01

The current study was undertaken to evaluate the clinical efficacy of end-threaded intramedullary pinning for management of various long bone fractures in canines. This study was conducted in two phases, managing 25 client-owned dogs presented with different fractures. The technique of application of end-threaded intramedullary pinning in long bone fractures was initially standardized in 6 clinical patients presented with long bone fractures. In this phase, end-threaded pins of different profiles, i.e., positive and negative, were used as the internal fixation technique. On the basis of results obtained from standardization phase, 19 client-owned dogs clinically presented with different fractures were implanted with end-threaded intramedullary positive profile screw ended self-tapping pin in the clinical application phase. The patients, allocated randomly in two groups, when evaluated postoperatively revealed slight pin migration in Group-I (negative profile), which resulted in disruption of callus site causing delayed union in one case and large callus formation in other two cases whereas no pin migration was observed in Group-II (positive profile). Other observations in Group-I was reduced muscle girth and delayed healing time as compared to Group-II. In clinical application, phase 21 st and 42 nd day post-operative radiographic follow-up revealed no pin migration in any of the cases, and there was no bone shortening or fragment collapse in end-threaded intramedullary positive profile screw ended self-tapping pin. The end-threaded intramedullary positive profile screw ended self-tapping pin used for fixation of long bone fractures in canines can resist pin migration, pin breakage, and all loads acting on the bone, i.e., compression, tension, bending, rotation, and shearing to an extent with no post-operative complications.

Direct bone morphogenetic protein 2 and Indian hedgehog gene transfer for articular cartilage repair using bone marrow coagulates.

PubMed

Sieker, J T; Kunz, M; Weißenberger, M; Gilbert, F; Frey, S; Rudert, M; Steinert, A F

2015-03-01

Bone morphogenetic protein 2 (BMP-2, encoded by BMP2) and Indian hedgehog protein (IHH, encoded by IHH) are well known regulators of chondrogenesis and chondrogenic hypertrophy. Despite being a potent chondrogenic factor BMP-2 was observed to induce chondrocyte hypertrophy in osteoarthritis (OA), growth plate cartilage and adult mesenchymal stem cells (MSCs). IHH might induce chondrogenic differentiation through different intracellular signalling pathways without inducing subsequent chondrocyte hypertrophy. The primary objective of this study is to test the efficacy of direct BMP2 and IHH gene delivery via bone marrow coagulates to influence histological repair cartilage quality in vivo. Vector-laden autologous bone marrow coagulates with 10(11) adenoviral vector particles encoding BMP2, IHH or the Green fluorescent protein (GFP) were delivered to 3.2 mm osteochondral defects in the trochlea of rabbit knees. After 13 weeks the histological repair cartilage quality was assessed using the ICRS II scoring system and the type II collagen positive area. IHH treatment resulted in superior histological repair cartilage quality than GFP controls in all of the assessed parameters (with P < 0.05 in five of 14 assessed parameters). Results of BMP2 treatment varied substantially, including severe intralesional bone formation in two of six joints after 13 weeks. IHH gene transfer is effective to improve repair cartilage quality in vivo, whereas BMP2 treatment, carried the risk intralesional bone formation. Therefore IHH protein can be considered as an attractive alternative candidate growth factor for further preclinical research and development towards improved treatments for articular cartilage defects. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Evidence for the adverse effect of starvation on bone quality: a review of the literature.

PubMed

Kueper, Janina; Beyth, Shaul; Liebergall, Meir; Kaplan, Leon; Schroeder, Josh E

2015-01-01

Malnutrition and starvation's possible adverse impacts on bone health and bone quality first came into the spotlight after the horrors of the Holocaust and the ghettos of World War II. Famine and food restrictions led to a mean caloric intake of 200-800 calories a day in the ghettos and concentration camps, resulting in catabolysis and starvation of the inhabitants and prisoners. Severely increased risks of fracture, poor bone mineral density, and decreased cortical strength were noted in several case series and descriptive reports addressing the medical issues of these individuals. A severe effect of severely diminished food intake and frequently concomitant calcium- and Vitamin D deficiencies was subsequently proven in both animal models and the most common cause of starvation in developed countries is anorexia nervosa. This review attempts to summarize the literature available on the impact of the metabolic response to Starvation on overall bone health and bone quality.

Bone health. New role for vitamin K?

PubMed Central

Ryan-Harshman, Milly; Aldoori, Walid

2004-01-01

OBJECTIVE: To assess growing evidence that vitamin K (phylloquinone) plays an important role in bone health and, subsequently, in prevention of osteoporotic fractures. QUALITY OF EVIDENCE: We searched MEDLINE from January 1972 to December 2002 using the key words vitamin K and bone health. We reviewed 30 articles that seemed relevant or had a human focus. All evidence can be categorized as level II. MAIN MESSAGE: Evidence suggests that dietary phylloquinone intake of <100 microg daily might not be optimal for bone health. Low intake of vitamin K could contribute to osteoporosis and subsequent fracture due to the undercarboxylation of osteocalcin. CONCLUSION: Family physicians need to be aware of the importance of encouraging adequate vitamin K intake, particularly among institutionalized elderly people, to prevent increased bone resorption. Further study is needed to determine the exact role of vitamin K in bone metabolism, and methods of assessing vitamin K requirements need to be standardized. PMID:15317231

In vivo outcomes of tissue-engineered osteochondral grafts.

PubMed

Bal, B Sonny; Rahaman, Mohamed N; Jayabalan, Prakash; Kuroki, Keiichi; Cockrell, Mary K; Yao, Jian Q; Cook, James L

2010-04-01

Tissue-engineered osteochondral grafts have been synthesized from a variety of materials, with some success at repairing chondral defects in animal models. We hypothesized that in tissue-engineered osteochondral grafts synthesized by bonding mesenchymal stem cell-loaded hydrogels to a porous material, the choice of the porous scaffold would affect graft healing to host bone, and the quality of cell restoration at the hyaline cartilage surface. Bone marrow-derived allogeneic mesenchymal stem cells were suspended in hydrogels that were attached to cylinders of porous tantalum metal, allograft bone, or a bioactive glass. The tissue-engineered osteochondral grafts, thus created were implanted into experimental defects in rabbit knees. Subchondral bone restoration, defect fill, bone ingrowth-implant integration, and articular tissue quality were compared between the three subchondral materials at 6 and 12 weeks. Bioactive glass and porous tantalum were superior to bone allograft in integrating to adjacent host bone, regenerating hyaline-like tissue at the graft surface, and expressing type II collagen in the articular cartilage.

Comparison of ADM and Connective Tissue Graft as the Membrane in Class II Furcation Defect Regeneration: A Randomized Clinical Trial

PubMed Central

Esfahanian, Vahid; Farhad, Shirin; Sadighi Shamami, Mehrnaz

2014-01-01

Background and aims. Furcally-involved teeth present unique challenges to the success of periodontal therapy and influence treatment outcomes. This study aimed to assess to compare use of ADM and connective tissue membrane in class II furcation defect regeneration. Materials and methods. 10 patient with 2 bilaterally class II furcation defects in first and/or second maxilla or man-dibular molar without interproximal furcation involvement, were selected. Four weeks after initial phase of treatment, before and thorough the surgery pocket depth (PD), clinical attachment level to stent (CAL-S), free gingival margin to stent(FGM-S) , crestal bone to stent (Crest-S), horizontal defect depth to stent (HDD-S) and vertical defect depth to stent (VDD-S) and crestal bone to defect depth measured from stent margin. Thereafter, one side randomly treated using connective tissue and DFDBA (study group) and opposite side received ADM and DFDBA (control group). After 6 months, soft and hard tissue parameters measured again in re-entry. Results. Both groups presented improvements after therapies (P & 0.05). No inter-group differences were seen in PD re-duction (P = 0.275), CAL gain (P = 0.156), free gingival margin (P = 0.146), crest of the bone (P = 0.248), reduction in horizontal defects depth (P = 0.139) and reduction in vertical defects depth (P = 0.149). Conclusion. Both treatments modalities have potential of regeneration without any adverse effect on healing process. Connective tissue grafts did not have significant higher bone fill compared to that of ADM. PMID:25093054

What Happens to bone health during and after spaceflight?

NASA Technical Reports Server (NTRS)

Sibonga, Jean D.; Evans, Harlan J.; Spector, Elisabeth R.; Maddocks, Mary J.; Smith, Scott A.; Shackelford, Linda C.; LeBlanc, Adrian D.

2006-01-01

Weightless conditions of space flight accelerate bone loss. There are no reports to date that address whether the bone that is lost during spaceflight could ever be recovered. Spaceinduced bone loss in astronauts is evaluated at the Johnson Space Center (JSC) by measurement of bone mineral density (BMD) by Dual-energy x-ray absorptiometry (DXA) scans. Astronauts are routinely scanned preflight and at various time points postflight (greater than or equal to Return+2 days). Two sets of BMD data were used to model spaceflight-induced loss and skeletal recovery in crewmembers following long-duration spaceflight missions (4-6 months). Group I was from astronauts (n=7) who were systematically scanned at multiple time points during the postflight period as part of a research protocol to investigate skeletal recovery. Group II came from a total of 49 sets of preflight and postflight data obtained by different protocols. These data were from 39 different crewmembers some of whom served on multiple flights. Changes in BMD (between pre- and postflight BMD) were plotted as a function of time (days-after-landing); plotted data were fitted to an exponential equation which enabled estimations of i) BMD change at day 0 after landing and ii) the number of days by which 50% of the lost bone is recovered (half-life). These fits were performed for BMD of the lumbar spine, trochanter, pelvis, femoral neck and calcaneus. There was consistency between the models for BMD recovery. Based upon the exponential model of BMD restoration, recovery following long-duration missions appears to be substantially complete in crewmembers within 36 months following return to Earth.

Bone-anchored intermaxillary elastics in an asymmetric Class II malocclusion: A case report.

PubMed

Manni, Antonio; Lupini, Daniela; Cozzani, Mauro

2017-06-01

A 13-year-old male patient, presenting a Class II, division 1 malocclusion and crowding was treated by an innovative technique. After rapid palatal expansion by a Hyrax appliance, the teeth were bonded with straightwire brackets. Two miniscrews were inserted, one per side, in the mandibular buccal bone between the roots of the mandibular first molar and the second premolar. On the right side, the miniscrew implant was connected to the hook clamped on a 0.021×0.028″ SS wire with a twisted SS ligature in order to maintain the inclination of the frontal incisors during the Class II mechanics. On the left side, where the Class II relationship was more marked, intermaxillary elastics were applied from the upper left hook clamped on the archwire to the lower first molar and a power chain (100g) was stretched from the lower left hook to the miniscrew implant. Class II correction was accomplished using sequential Class II elastics of progressive strength coupled with rectangular stainless steel wires. After 22 months of active treatment, the results were balanced facial esthetics and a good occlusion. This dual anchorage set-up of Class II elastics reinforced with TADs produced protrusive action on the mandible with minimal side effects and with no significant change in the vertical dimension during the sagittal correction of the Class II malocclusion. Copyright © 2017 CEO. Published by Elsevier Masson SAS. All rights reserved.

Increased formation of autophagosomes in ectromelia virus-infected primary culture of murine bone marrow-derived macrophages.

PubMed

Martyniszyn, L; Szulc-Dąbrowska, L; Boratyńska-Jasińska, A; Niemiałtowski, M

2013-01-01

Induction of autophagy by ectromelia virus (ECTV) in primary cultures of bone marrow-derived macrophages (BMDMs) was investigated. The results showed that ECTV infection of BMDMs resulted in increased formation of autophagosomes, increased level of LC3-II protein present in aggregates and extensive cytoplasmic vacuolization. These data indicate an increased autophagic activity in BMDMs during ECTV infection.

Wrapping grafting for congenital pseudarthrosis of the tibia

PubMed Central

Yan, An; Mei, Hai-Bo; Liu, Kun; Wu, Jiang-Yan; Tang, Jin; Zhu, Guang-Hui; Ye, Wei-Hua

2017-01-01

Abstract Objective: Treatment of congenital pseudarthrosis of the tibia (CPT) remains a challenge. The autogenic iliac bone graft is important consistent of treatment for CPT. The purpose of this study was to investigate the role of wrapping autogenic iliac bone graft in improvement of the curing opportunities of CPT. Methods: We combined Ilizarov fixator with intramedullary rodding of the tibia and wrapping autogenic iliac bone graft for treatment 51 cases of CPT between 2007 and 2010. The mean age is 3.2 years at index operation, of which 31 patients (61%) were below 3 years old. According to Crawford classification, 5 tibia had type-II morphology; 3, type-III; 43, type-IV. Results: In the postoperative follow-up of 3.5 months (range from 3 to 4.5 months), all cases were found that the bone graft sites of pseudarthrosis of the tibia showed a significant augmentation and spindle-shaped expansion as obvious change. All cases of this series have been followed-up, average followed-up time were 1.6 years (range from 7 to 3.1 years), of which 19 cases were more than 2 years. The average time of removed the Ilizarov ring fixator was 3.5 months (range from 3 to 4.5 months). According to Johnston Clinical evaluation system, 26 cases had grade I, 21 cases, grade II, 4 cases, grade III. Following the Ohnishi X-ray evaluation criteria, union of pseudarthrosis of the tibia were 42 cases, delayed union 5 cases, nonunion 4 cases. Conclusion: Autogenic iliac bone graft is able to offer the activity of osteoblasts and osteogenesis induced by bone morphogenetic protein (BMP) and glycoprotein, meanwhile enclosing bone graft could help keep cancellous bone fragments in close contact around pseudarthrosis of the tibia, allowing the formation of high concentration of glycoprotein and BMP induced by chemical factors because of established the sealing environment in location, all of which could enhance the healing of pseudarthrosis of the tibia. PMID:29310362

Progress in the research on the mechanism of bone metastasis in lung cancer

PubMed Central

Luo, Qinqin; Xu, Zhenye; Wang, Lifang; Ruan, Mingyu; Jin, Guiyu

2016-01-01

Lung cancer is still the predominant cause of cancer-associated mortality worldwide. The bone metastasis of lung cancer brings great suffering to the patient. Previous advances have provided insights into the mechanism of bone metastasis. Previous research has investigated lung cancer stem cells and three steps were determined for the lung cancer cells to metastasize to the bone: i) Escaping from the primary tumor; ii) moving in the circulation; iii) colonizing in the bone. Key molecules are involved in each of these process. Although there is a close association and similarity, dynamic microenvironments affect these processes. The receptor activator of nuclear factor-κB (RANK)/RANKL axis serves a vital role in the regulation of the generation and activation of osteoclasts during the osteolytic lesion. However, the specific molecules for the lung cancer cells to metastasize to the bone require further research and exploration. The present study aimed to investigate the relative molecular mechanisms of bone metastasis in lung cancer in recent years, providing a general understanding about the features of lung cancer preferences to bone, and discussing other things that require investigation. PMID:27446555

The selective cathepsin K inhibitor MIV-711 attenuates joint pathology in experimental animal models of osteoarthritis.

PubMed

Lindström, Erik; Rizoska, Biljana; Tunblad, Karin; Edenius, Charlotte; Bendele, Alison M; Maul, Don; Larson, Michael; Shah, Neha; Yoder Otto, Valerie; Jerome, Chris; Grabowska, Urszula

2018-03-09

MIV-711 is a highly potent and selective cathepsin K inhibitor. The current article summarizes the therapeutic effects of MIV-711 on joint pathology in rabbits subjected to anterior cruciate ligament transection (ACLT), and the prophylactic effects on joint pathology in dogs subjected to partial medial meniscectomy, two surgical models of osteoarthritis (OA). Starting 1 week after surgery, rabbits were dosed daily via oral gavage with either MIV-711 or vehicle (n = 7/group) for 7 weeks. The four treatment groups were: (1) sham + vehicle; (2) ACLT + vehicle; (3) ACLT + MIV-711, 30 µmol/kg and (4) ACLT + MIV-711, 100 µmol/kg. Subchondral bone and articular cartilage structures were assessed by µCT, histomorphometry, and scoring. Dogs subjected to partial medial meniscectomy received either MIV-711 (30 µmol/kg) or vehicle (n = 15/group) via oral gavage once daily, starting 1 day before meniscectomy, for 28 days. Cartilage degradation was assessed at the macroscopic and microscopic levels. The exposures of MIV-711 were assessed in both studies and biomarkers reflecting bone resorption (HP-1 in rabbits, CTX-I in dogs) and cartilage degradation (CTX-II) were measured. In ACLT rabbits, MIV-711 decreased HP-1 levels by up to 72% (p < 0.001) and CTX-II levels by up to 74% (p < 0.001) compared to ACLT vehicle controls. ACLT surgery significantly reduced the total thickness of the subchondral bone plate and reduced trabecular bone volume in the femur and tibia. These effects were reversed by MIV-711. ACLT resulted in cartilage thickening, which was attenuated by MIV-711. MIV-711 did not affect osteophyte formation or Mankin scores. In dogs, MIV-711 reduced CTX-I and CTX-II levels by 86% (p < 0.001) and 80% (p < 0.001), respectively. Synovial CTX-II levels were reduced by 55-57% (p < 0.001) compared to baseline. MIV-711-treated animals had 25-37% lower macroscopic scores in the femur condyles and 13-33% lower macroscopic scores in the tibial plateaus. MIV-711 prevents subchondral bone loss and partially attenuates cartilage pathology in two animal models of OA. These beneficial effects of MIV-711 on joint pathology are observed in conjunction with decreases in bone and cartilage biomarkers that have been shown to be clinically attainable in human. The data support the further development of MIV-711 for the treatment of OA.

Indian girls have higher bone mineral content per unit of lean body than boys through puberty.

PubMed

Khadilkar, Anuradha V; Sanwalka, Neha; Mughal, M Zulf; Chiplonkar, Shashi; Khadilkar, Vaman

2018-05-01

Our aim is to describe changes in the muscle-bone unit assessed as a ratio of bone mineral content (BMC) to lean body mass (LBM) through puberty at total body and various skeletal sites in Indian boys and girls. A cross-sectional study was conducted (888 children, 480 boys, aged 5-17 years) in Pune, India. Pubertal staging was assessed. BMC, LBM and fat percentage at the arms, legs, android, gynoid and total body (less the head) were assessed by dual energy X-ray absorptiometry. The amount of BMC per unit LBM (BMC/LBM) was computed. Changes in mean BMC/LBM at 5 Tanner (pubertal) stages after adjustment for age and fat percentage were calculated. In boys, adjusted BMC/LBM was significantly higher with successive Tanner stages [legs (TS-II vs TS-I), android (TS-III vs TS-II, TS-IV vs TS-III) and gynoid region (TS-III vs TS-II and TS-II vs TS-I) (p < 0.05)]. In girls, adjusted BMC/LBM was significantly higher with successive Tanner stages at total body, legs and gynoid (TS-III vs TS-II; TS-II vs TS-I; TS-V vs TS-IV), arms (TS-I to TS-V) and android regions (TS-V vs TS-IV) (p < 0.05). Boys had significantly higher adjusted BMC/LBM than girls at earlier Tanner stages (TS-I to TS-III), whereas girls had significantly higher adjusted BMC/LBM than boys at later Tanner stages (TS-IV, TS-V) (p < 0.05). Indian boys and girls showed higher total and regional body, and age- and fat percentage-adjusted BMC/LBM with successive pubertal stages. Girls had higher BMC/LBM than boys which may possibly act as a reservoir for later demands of pregnancy and lactation.

Treatment for unicameral bone cysts in long bones: an evidence based review.

PubMed

Donaldson, Sandra; Chundamala, Josie; Yandow, Suzanne; Wright, James G

2010-03-20

The purpose of this paper is to perform an evidence based review for treatment of unicameral bone cysts. A search of MEDLINE (1966 to 2009) was conducted and the studies were classified according to levels of evidence. This review includes only comparative Level I-III studies. The systematic review identified 16 studies. There is one level I study, one level II study and the remaining 14 studies are level III. Seven of the sixteen studies had statistically different results: three studies indicated that steroid injection was superior to bone marrow injection or curettage and bone grafting; one study indicated that cannulated screws were superior to steroid injections; one study indicated resection and myoplasty was superior to steroid injection; one study indicated a combination of steroid, demineralized bone matrix and bone marrow aspirate, and curettage and bone grafting were superior to steroid injection; and one study indicated that curettage and bone grafting was superior to non-operative immobilization. Based on one Level I study, including a limited number of individuals, steroid injection seems to be superior to bone marrow injection. As steroid injections have already demonstrated superiority over bone marrow injections in a randomized clinical trial, the next step would be a prospective trial comparing steroid injections with other treatments.

Treatment for unicameral bone cysts in long bones: an evidence based review

PubMed Central

Donaldson, Sandra; Chundamala, Josie; Yandow, Suzanne; Wright, James G.

2010-01-01

The purpose of this paper is to perform an evidence based review for treatment of unicameral bone cysts. A search of MEDLINE (1966 to 2009) was conducted and the studies were classified according to levels of evidence. This review includes only comparative Level I-III studies. The systematic review identified 16 studies. There is one level I study, one level II study and the remaining 14 studies are level III. Seven of the sixteen studies had statistically different results: three studies indicated that steroid injection was superior to bone marrow injection or curettage and bone grafting; one study indicated that cannulated screws were superior to steroid injections; one study indicated resection and myoplasty was superior to steroid injection; one study indicated a combination of steroid, demineralized bone matrix and bone marrow aspirate, and curettage and bone grafting were superior to steroid injection; and one study indicated that curettage and bone grafting was superior to non-operative immobilization. Based on one Level I study, including a limited number of individuals, steroid injection seems to be superior to bone marrow injection. As steroid injections have already demonstrated superiority over bone marrow injections in a randomized clinical trial, the next step would be a prospective trial comparing steroid injections with other treatments. PMID:21808696

Repatriation and Identification of Finnish World War II Soldiers

PubMed Central

Palo, Jukka U.; Hedman, Minttu; Söderholm, Niklas; Sajantila, Antti

2007-01-01

Aim To present a summary of the organization, field search, repatriation, forensic anthropological examination, and DNA analysis for the purpose of identification of Finnish soldiers with unresolved fate in World War II. Methods Field searches were organized, executed, and financed by the Ministry of Education and the Association for Cherishing the Memory of the Dead of the War. Anthropological examination conducted on human remains retrieved in the field searches was used to establish the minimum number of individuals and description of the skeletal diseases, treatment, anomalies, or injuries. DNA tests were performed by extracting DNA from powdered bones and blood samples from relatives. Mitochondrial DNA (mtDNA) sequence comparisons, together with circumstantial evidence, were used to connect the remains to the putative family members. Results At present, the skeletal remains of about a thousand soldiers have been found and repatriated. In forensic anthropological examination, several injuries related to death were documented. For the total of 181 bone samples, mtDNA HVR-1 and HVR-2 sequences were successfully obtained for 167 (92.3%) and 148 (81.8%) of the samples, respectively. Five samples yielded no reliable sequence data. Our data suggests that mtDNA preserves at least for 60 years in the boreal acidic soil. The quality of the obtained mtDNA sequence data varied depending on the sample bone type, with long compact bones (femur, tibia and humerus) having significantly better (90.0%) success rate than other bones (51.2%). Conclusion Although more than 60 years have passed since the World War II, our experience is that resolving the fate of soldiers missing in action is still of uttermost importance for people having lost their relatives in the war. Although cultural and individual differences may exist, our experience presented here gives a good perspective on the importance of individual identification performed by forensic professionals. PMID:17696308

Sex-related differences of bone properties of pelvic limb and bone metabolism indices in 14-month-old ostriches (Struthio camelus).

PubMed

Krupski, W; Tatara, M R; Charuta, A; Brodzki, A; Szpetnar, M; Jóźwik, A; Strzałkowska, N; Poławska, E; Łuszczewska-Sierakowska, I

2018-06-01

1. Sex-related differences of long pelvic limb bones and serum bone metabolism indices were evaluated in 14-month-old female (N = 7) and male (N = 7) ostriches of similar body weights. 2. Densitometric parameters of femur, tibia and tarsometatarsus were determined using quantitative computed tomography (volumetric bone mineral density, calcium hydroxyapatite density and mean volumetric bone mineral density) and dual energy X-ray absorptiometry (bone mineral density and bone mineral content) methods. Geometrical parameters such as cortical bone area, cross-sectional area, second moment of inertia, mean relative wall thickness and cortical index were determined in the midshaft of bones. Mechanical properties of bones (maximum elastic strength and ultimate strength) were evaluated using three-point bending test. Serum concentrations of free amino acids, osteocalcin, N-terminal propeptide of type I procollagen, C-terminal telopeptides of type II collagen and total antioxidative capacity were also determined. 3. Bone weight and relative bone weight of all bones were significantly higher in males than in females. Significantly lower values of trabecular bone mineral density and calcium hydroxyapatite density were found in the trabecular bone of tibia in males. The highest number of the sex-related differences was observed in the tarsometatarsus where bone length, bone mineral content, cortical bone area, cross-sectional area and ultimate strength were higher in males. Serum concentrations of taurine, hydroxyproline, valine and isoleucine were significantly higher in males. 4. Higher loading of the tarsometatarsus in comparison to femur and tibia may be an important factor interacting with sex hormones in regulation of bone formation and mineralisation processes. Sex-related differences of bone properties were associated with increased serum concentration of selected amino acids in males.

Overexpression of MicA induces production of OmpC-enriched outer membrane vesicles that protect against Salmonella challenge.

PubMed

Choi, Hyun-Il; Kim, Moonjeong; Jeon, Jinseong; Han, Jin Kwan; Kim, Kwang-Sun

2017-08-26

Outer membrane vesicles (OMVs) derived from bacteria are promising candidates for subunit vaccines. Stresses that modulate the composition of outer membrane proteins (OMPs) are important for OMV synthesis. Small RNAs (sRNAs) expressed in response to stress regulate OMPs, although the mechanism underlying sRNA-mediated OMV biogenesis and its utility for developing vaccine platforms remains to be elucidated. Here, we characterized the role of a sRNA, MicA, which regulates OmpA, a major OMP involved in both production of OMVs and reactive immunity against Salmonella challenge. A Salmonella strain overexpressing MicA generated more OMVs than a control strain. In addition, OmpC was the major component of MicA-derived OMV proteins. MicA-derived OMVs induced Th1- and Th17-type immune responses in vitro and reduced Salmonella-mediated lethality in a mouse model. Thus, OmpA-regulatory sRNA-derived OMVs may facilitate production of Salmonella-protective vaccines. Copyright © 2017 Elsevier Inc. All rights reserved.

Can the pattern of vertebral marrow oedema differentiate intervertebral disc infection from degenerative changes?

PubMed

Shrot, S; Sayah, A; Berkowitz, F

2017-07-01

To evaluate whether various patterns of bone marrow oedema could be used to discriminate between infection and degenerative change. Seventy patients with imaging features suspicious for discitis and available clinical follow-up were blindly reviewed for vertebral marrow oedema on sagittal short-tau inversion recovery (STIR) images according to the following patterns: I, vertebra oedema is adjacent to the intervertebral space and sharply-marginated; II, vertebral oedema is adjacent to the intervertebral space but not sharply marginated from normal marrow or involves the entire vertebral body; and III, vertebral oedema is distant from the endplate with intervening hypointense marrow signal. Of 45 patients with a clinical diagnosis of discitis, pattern II was the most common oedema pattern (64%). Approximately 20% and 9% of discitis patients showed patterns I and III, respectively. In patients with degenerative changes, 44% patients showed pattern I, 32% showed pattern II, and 24% showed pattern III. Pattern II had a sensitivity, specificity, and positive predictive value of 0.64, 0.68, and 0.78 for diagnosing spine infection, respectively. Although bone marrow oedema in infective discitis most often extends from the disc space and has indistinct margins, the oedema may also have sharp margins or be remote from the involved intervertebral space. Bone marrow oedema patterns of infective discitis overlap with those of degenerative disease and are not sufficiently reliable to exclude infection in cases with magnetic resonance imaging findings suggestive of discitis. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Role of the greater sciatic notch of the hip bone in sexual dimorphism: a morphometric study of the north Indian population.

PubMed

G, Kalsey; R K, Singla; K, Sachdeva

2011-04-01

The distinctive morphology and sexual dimorphism of the human hip bone makes it of interest from the anatomical, anthropological and forensic points of view. The shape of the greater sciatic notch has attracted great attention in the past. In the current investigation, an attempt has been made to find the baseline data of various parameters pertaining to the greater sciatic notch of 100 hip bones of known sex (male:female = 80:20) and side (right:left = 50:50), obtained from the Department of Anatomy, Government Medical College, Amritsar, Punjab, India, during the period 2007-2009. Seven parameters of the notch, viz. width, depth, posterior segment width, total angle, posterior segment angle, index I and index II of the greater sciatic notch were studied. The results thus obtained were compiled, tabulated, statistically analysed and were compared with the accessible literature. Out of all the parameters studied, width of the notch, posterior segment width, total angle, posterior segment angle and index II of notch were found to be significantly greater in women as compared with men. Thus the greater sciatic notch can serve as a reliable sex indicator even when the complete hip bone has not been well preserved.

Specific Dioscorea Phytoextracts Enhance Potency of TCL-Loaded DC-Based Cancer Vaccines

PubMed Central

Chang, Wei-Ting; Chen, Hui-Ming; Yin, Shu-Yi; Chen, Yung-Hsiang; Wen, Chih-Chun; Wei, Wen-Chi; Lai, Phoency; Wang, Cheng-Hsin; Yang, Ning-Sun

2013-01-01

Dioscorea tuber phytoextracts can confer immunomodulatory activities ex vivo and improve regeneration of bone marrow cells in vivo. In present study, we evaluated specific Dioscorea phytoextracts for use ex vivo as a bone-marrow-derived dendritic cell- (DC-) based vaccine adjuvant for cancer immunotherapy. Fractionated Dioscorea extracts (DsII) were assayed for their effect on maturation and functions of DC ex vivo and antimelanoma activity of DC-based vaccine in vivo. The phytoextract from 50–75% ethanol-precipitated fraction of Dioscorea alata var. purpurea Tainung no. 5 tuber, designated as DsII-TN5, showed a strong augmentation of tumor cell lysate- (TCL-) loaded DC-mediated activation of T-cell proliferation. DsII-TN5 stimulated the expression of CD40, CD80, CD86, and IL-1β in TCL-loaded DCs and downregulated the expression of TGF-β1. DC vaccines prepared by a specific schema (TCL (2 h) + LPS (22 h)) showed the strongest antitumor activity. DsII-TN5 as a DC vaccine adjuvant showed strong antimelanoma activity and reduced myeloid-derived suppressor cell (MDSC) population in tested mice. DsII-TN5 can also activate DCs to enhance Th1- and Th17-related cytokine expressions. Biochemical analysis showed that DsII-TN5 consists mainly of polysaccharides containing a high level (53%) of mannose residues. We suggest that DsII-TN5 may have potential for future application as a potent, cost-effective adjuvant for DC-based cancer vaccines. PMID:23935688

Evidence for the Adverse Effect of Starvation on Bone Quality: A Review of the Literature

PubMed Central

Kueper, Janina; Beyth, Shaul; Liebergall, Meir; Kaplan, Leon; Schroeder, Josh E.

2015-01-01

Malnutrition and starvation's possible adverse impacts on bone health and bone quality first came into the spotlight after the horrors of the Holocaust and the ghettos of World War II. Famine and food restrictions led to a mean caloric intake of 200–800 calories a day in the ghettos and concentration camps, resulting in catabolysis and starvation of the inhabitants and prisoners. Severely increased risks of fracture, poor bone mineral density, and decreased cortical strength were noted in several case series and descriptive reports addressing the medical issues of these individuals. A severe effect of severely diminished food intake and frequently concomitant calcium- and Vitamin D deficiencies was subsequently proven in both animal models and the most common cause of starvation in developed countries is anorexia nervosa. This review attempts to summarize the literature available on the impact of the metabolic response to Starvation on overall bone health and bone quality. PMID:25810719

Inhibition of TGF–β signaling in subchondral bone mesenchymal stem cells attenuates osteoarthritis

PubMed Central

Zhen, Gehua; Wen, Chunyi; Jia, Xiaofeng; Li, Yu; Crane, Janet L.; Mears, Simon C.; Askin, Frederic B.; Frassica, Frank J.; Chang, Weizhong; Yao, Jie; Nayfeh, Tariq; Johnson, Carl; Artemov, Dmitri; Chen, Qianming; Zhao, Zhihe; Zhou, Xuedong; Cosgarea, Andrew; Carrino, John; Riley, Lee; Sponseller, Paul; Wan, Mei; Lu, William Weijia; Cao, Xu

2013-01-01

Osteoarthritis is a highly prevalent and debilitating joint disorder. There is no effective medical therapy for osteoarthritis due to limited understanding of osteoarthritis pathogenesis. We show that TGF–β1 is activated in the subchondral bone in response to altered mechanical loading in an anterior cruciate ligament transection (ACLT) osteoarthritis mouse model. TGF–β1 concentrations also increased in human osteoarthritis subchondral bone. High concentrations of TGF–β1 induced formation of nestin+ mesenchymal stem cell (MSC) clusters leading to aberrant bone formation accompanied by increased angiogenesis. Transgenic expression of active TGF–β1 in osteoblastic cells induced osteoarthritis. Inhibition of TGF–β activity in subchondral bone attenuated degeneration of osteoarthritis articular cartilage. Notably, knockout of the TGF–β type II receptor (TβRII) in nestin+ MSCs reduced development of osteoarthritis in ACLT mice. Thus, high concentrations of active TGF–β1 in the subchondral bone initiated the pathological changes of osteoarthritis, inhibition of which could be a potential therapeutic approach. PMID:23685840

Effect of a Rapidly Degrading Presolidified 10 kDa Chitosan/Blood Implant and Subchondral Marrow Stimulation Surgical Approach on Cartilage Resurfacing in a Sheep Model.

PubMed

Bell, Angela D; Hurtig, Mark B; Quenneville, Eric; Rivard, Georges-Étienne; Hoemann, Caroline D

2017-10-01

Objective This study tested the hypothesis that presolidified chitosan-blood implants are retained in subchondral bone channels perforated in critical-size sheep cartilage defects, and promote bone repair and hyaline-like cartilage resurfacing versus blood implant. Design Cartilage defects (10 × 10 mm) with 3 bone channels (1 drill, 2 Jamshidi biopsy, 2 mm diameter), and 6 small microfracture holes were created bilaterally in n = 11 sheep knee medial condyles. In one knee, 10 kDa chitosan-NaCl/blood implant (presolidified using recombinant factor VIIa or tissue factor), was inserted into each drill and Jamshidi hole. Contralateral knee defects received presolidified whole blood clot. Repair tissues were assessed histologically, biochemically, biomechanically, and by micro-computed tomography after 1 day ( n = 1) and 6 months ( n = 10). Results Day 1 defects showed a 60% loss of subchondral bone plate volume fraction along with extensive subchondral hematoma. Chitosan implant was resident at day 1, but had no effect on any subsequent repair parameter compared with blood implant controls. At 6 months, bone defects exhibited remodeling and hypomineralized bone repair and were partly resurfaced with tissues containing collagen type II and scant collagen type I, 2-fold lower glycosaminoglycan and fibril modulus, and 4.5-fold higher permeability compared with intact cartilage. Microdrill holes elicited higher histological ICRS-II overall assessment scores than Jamshidi holes (50% vs. 30%, P = 0.041). Jamshidi biopsy holes provoked sporadic osteonecrosis in n = 3 debrided condyles. Conclusions Ten kilodalton chitosan was insufficient to improve repair. Microdrilling is a feasible subchondral marrow stimulation surgical approach with the potential to elicit poroelastic tissues with at least half the compressive modulus as intact articular cartilage.

Effect of a Rapidly Degrading Presolidified 10 kDa Chitosan/Blood Implant and Subchondral Marrow Stimulation Surgical Approach on Cartilage Resurfacing in a Sheep Model

PubMed Central

Bell, Angela D.; Hurtig, Mark B.; Quenneville, Eric; Rivard, Georges-Étienne; Hoemann, Caroline D.

2016-01-01

Objective This study tested the hypothesis that presolidified chitosan-blood implants are retained in subchondral bone channels perforated in critical-size sheep cartilage defects, and promote bone repair and hyaline-like cartilage resurfacing versus blood implant. Design Cartilage defects (10 × 10 mm) with 3 bone channels (1 drill, 2 Jamshidi biopsy, 2 mm diameter), and 6 small microfracture holes were created bilaterally in n = 11 sheep knee medial condyles. In one knee, 10 kDa chitosan–NaCl/blood implant (presolidified using recombinant factor VIIa or tissue factor), was inserted into each drill and Jamshidi hole. Contralateral knee defects received presolidified whole blood clot. Repair tissues were assessed histologically, biochemically, biomechanically, and by micro–computed tomography after 1 day (n = 1) and 6 months (n = 10). Results Day 1 defects showed a 60% loss of subchondral bone plate volume fraction along with extensive subchondral hematoma. Chitosan implant was resident at day 1, but had no effect on any subsequent repair parameter compared with blood implant controls. At 6 months, bone defects exhibited remodeling and hypomineralized bone repair and were partly resurfaced with tissues containing collagen type II and scant collagen type I, 2-fold lower glycosaminoglycan and fibril modulus, and 4.5-fold higher permeability compared with intact cartilage. Microdrill holes elicited higher histological ICRS-II overall assessment scores than Jamshidi holes (50% vs. 30%, P = 0.041). Jamshidi biopsy holes provoked sporadic osteonecrosis in n = 3 debrided condyles. Conclusions Ten kilodalton chitosan was insufficient to improve repair. Microdrilling is a feasible subchondral marrow stimulation surgical approach with the potential to elicit poroelastic tissues with at least half the compressive modulus as intact articular cartilage. PMID:28934884

A study of the kinetics and isotherms for Cr(VI) adsorption in a binary mixture of Cr(VI)-Ni(II) using hierarchical porous carbon obtained from pig bone.

PubMed

Li, Chengxian; Huang, Zhe; Huang, Bicheng; Liu, Changfeng; Li, Chengming; Huang, Yaqin

2014-01-01

Cr(VI) adsorption in a binary mixture Cr(VI)-Ni(II) using the hierarchical porous carbon prepared from pig bone (HPC) was investigated. The various factors affecting adsorption of Cr(VI) ions from aqueous solutions such as initial concentration, pH, temperature and contact time were analyzed. The results showed excellent efficiency of Cr(VI) adsorption by HPC. The kinetics and isotherms for Cr(VI) adsorption from a binary mixture Cr(VI)-Ni(II) by HPC were studied. The adsorption equilibrium described by the Langmuir isotherm model is better than that described by the Freundlich isotherm model for the binary mixture in this study. The maximum adsorption capacity was reliably found to be as high as 192.68 mg/g in the binary mixture at pH 2. On fitting the experimental data to both pseudo-first- and second-order equations, the regression analysis of the second-order equation gave a better R² value.

Bolus administration of steroid therapy is more favorable than the conventional use in preventing decrease of bone density and the increase of body fat percentage in patients with inflammatory bowel disease.

PubMed

Farkas, Klaudia; Bálint, Anita; Valkusz, Zsuzsanna; Szepes, Zoltán; Nagy, Ferenc; Szűcs, Mónika; Bor, Renáta; Wittmann, Tibor; Molnár, Tamás

2014-09-01

The effects of short course of corticosteroids on the metabolic processes and bone formation has not been well studied. Our aim was to compare the efficacy, the side effects and the bone and lipid metabolisms in IBD patients using bolus or conventional tapering of methylprednisolone for 12 weeks. Nineteen IBD patients received intravenous methylprednisolone of 1mg/kg for 5 days tapered by 4 mg per week. Patients were prospectively randomized in two groups. In "conventional" group (I) steroids were given daily. In "pulse" group (II) weekly doses of steroids were given on special days of the week. The body mass index (BMI) was measured before and after the corticosteroid therapy. Blood samples were collected to assess glucose level, electrolytes, cholesterol and triglyceride levels, inflammatory parameters, cortisol, osteocalcin and crosslaps values. Total body composition analysis was performed at the beginning and at the end of the steroid therapy. In Group I, BMI increased, total body bone density decreased significantly at the end of the steroid therapy. Body fat percent showed a tendency to be higher at the end of steroid therapy in Group I. Cholesterol level increased significantly in Group I patients. The decrease in serum cortisol level was more remarkable in Group I vs. Group II after steroid therapy. Less side-effect occurred in Group II vs. Group I. Our results suggest that bolus tapering of corticosteroids may have more favorable short term outcome than conventional tapering that may revolutionize steroid therapy in IBD. Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Inhibition of cathepsin K reduces cartilage degeneration in the anterior cruciate ligament transection rabbit and murine models of osteoarthritis.

PubMed

Hayami, Tadashi; Zhuo, Ya; Wesolowski, Gregg A; Pickarski, Maureen; Duong, Le T

2012-06-01

To investigate the disease modifying effects of cathepsin K (CatK) inhibitor L-006235 compared to alendronate (ALN) in two preclinical models of osteoarthritis (OA). Skeletally mature rabbits underwent sham or anterior cruciate ligament transection (ACLT)-surgery and were treated with L-006235 (L-235, 10 mg/kg or 50 mg/kg, p.o., daily) or ALN (0.6 mg/kg, s.c., weekly) for 8-weeks. ACLT joint instability was also induced in CatK(-/-) versus wild type (wt) mice and treated for 16-weeks. Changes in cartilage degeneration, subchondral bone volume and osteophyte area were determined by histology and μ-CT. Collagen type I helical peptide (HP-I), a bone resorption marker and collagen type II C-telopeptide (CTX-II), a cartilage degradation marker were measured. L-235 (50 mg/kg) and ALN treatment resulted in significant chondroprotective effects, reducing CTX-II by 60% and the histological Mankin score for cartilage damage by 46% in the ACLT-rabbits. Both doses of L-235 were more potent than ALN in protecting against focal subchondral bone loss, and reducing HP-I by 70% compared to vehicle. L-235 (50 mg/kg) and ALN significantly reduced osteophyte formation in histomorphometric analysis by 55%. The Mankin score in ACLT-CatK(-/-) mice was ~2.5-fold lower than the ACLT-wt mice and was not different from sham-CatK(-/-). Osteophyte development was not different among the groups. Inhibition of CatK provides significant benefits in ACLT-model of OA, including: 1) protection of subchondral bone integrity, 2) protection against cartilage degradation and 3) reduced osteophytosis. Preclinical evidence supports the role of CatK as a potential therapeutic target for the treatment of OA. Copyright © 2012 Elsevier Inc. All rights reserved.

Modeling corticosteroid effects in a rat model of rheumatoid arthritis II: mechanistic pharmacodynamic model for dexamethasone effects in Lewis rats with collagen-induced arthritis.

PubMed

Earp, Justin C; Dubois, Debra C; Molano, Diana S; Pyszczynski, Nancy A; Almon, Richard R; Jusko, William J

2008-08-01

A mechanism-based model for pharmacodynamic effects of dexamethasone (DEX) was incorporated into our model for arthritis disease progression in the rat to aid in identification of the primary factors responsible for edema and bone loss. Collagen-induced arthritis was produced in male Lewis rats after injection of type II porcine collagen. DEX was given subcutaneously in single doses of 0.225 or 2.25 mg/kg or 7-day multiple doses of 0.045 or 0.225 mg/kg at 21 days postdisease induction. Effects on disease progression were measured by paw swelling, bone mineral density (BMD), body weights, plasma corticosterone (CST), and tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and glucocorticoid receptor (GR) mRNA expression in paw tissue. Lumbar and femur BMD was determined by PIXImus II dual-energy X-ray absorptiometry. Plasma CST was assayed by high-performance liquid chromatography. Cytokine and GR mRNA were assayed by quantitative real-time polymerase chain reaction. Indirect response models, drug interaction models, transduction processes, and the fifth-generation model of corticosteroid dynamics were integrated and applied using S-ADAPT software to describe how dexamethasone binding to GR can regulate diverse processes. Cytokine mRNA, GR mRNA, plasma CST, and paw edema were suppressed after DEX administration. TNF-alpha mRNA expression and BMD seemed to increase immediately after dosing but were ultimately reduced. Model parameters indicated that IL-6 and IL-1beta were most sensitive to inhibition by DEX. TNF-alpha seemed to primarily influence edema, whereas IL-6 contributed the most to bone loss. Lower doses of corticosteroids may be sufficient to suppress the cytokines most relevant to bone erosion.

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

Tu Qisheng; Valverde, Paloma; Chen, Jake

Osterix (Osx) is a zinc-finger-containing transcription factor that is expressed in osteoblasts of all endochondral and membranous bones. In Osx null mice osteoblast differentiation is impaired and bone formation is absent. In this study, we hypothesized that overexpression of Osx in murine bone marrow stromal cells (BMSC) would be able to enhance their osteoblastic differentiation and mineralization in vitro. Retroviral transduction of Osx in BMSC cultured in non-differentiating medium did not affect expression of Runx2/Cbfa1, another key transcription factor of osteoblast differentiation, but induced an increase in the expression of other markers associated with the osteoblastic lineage including alkaline phosphatase,more » bone sialoprotein, osteocalcin, and osteopontin. Retroviral transduction of Osx in BMSC also increased their proliferation, alkaline phosphatase activity, and ability to form bone nodules. These events occurred without significant changes in the expression of {alpha}1(II) procollagen or lipoprotein lipase, which are markers of chondrogenic and adipogenic differentiation, respectively.« less

Hierarchy effect on electronic structure and core-to-valence transitions in bone tissue: perspectives in medical nanodiagnostics of mineralized bone

NASA Astrophysics Data System (ADS)

Samoilenko, Dmitrii O.; Avrunin, Alexander S.; Pavlychev, Andrey A.

2017-06-01

Electronic structure and core-to-valence transitions in bone tissue are examined in the framework of the morphological 3DSL model that takes into account (i) structural and functional organization of the skeleton in the normal and pathological conditions and (ii) peculiarities of electron wave propagation in a three-dimensional superlattice of "black-nanocrystallites-in-muddy-waters". Our focus is on the HAP-to-bone red shifts of core-to-valence transitions near Ca and P 2p and O 1s edges in single-crystal hydroxyapatite (HAP) Ca10(PO4)6(OH)2. The origin of the HAP-to-bone shift is discussed and the extended comparative analysis of the experimental data is performed. The detected spectral shift is assigned with the effect of hierarchical organization of bone tissue. This hierarchy effect on the core-to-valence transition energies is regarded as a promising tool for medical imaging and perspective pathway for nanodiagnostics of mineralized bone. Contribution to the Topical Issue "Dynamics of Systems at the Nanoscale", edited by Andrey Solov'yov and Andrei Korol.

Use of ossein-hydroxyapatite complex in the prevention of bone loss: a review.

PubMed

Castelo-Branco, C; Dávila Guardia, J

2015-02-01

The ossein-hydroxyapatite complex (OHC) is a microcrystalline form of calcium which provides a number of additional minerals (magnesium, phosphorus, potassium, zinc), and proteins (osteocalcin, type I collagen, type I insulin growth factor I and II, transforming growth factor beta) associated with bone metabolism. The objective of this review is to examine the role of OHC in preventing bone loss in different conditions. A review of clinical trials assessing the relationship between OHC and bone loss was made using the following data sources: Medline (from 1966 to December 2013), the Cochrane Controlled Clinical Trials Register, Embase (up to December 2013), contact with companies marketing the supplements studied, and reference lists. Different randomized, clinical trials and meta-analysis suggest that OHC is more effective than calcium supplements in maintaining bone mass in postmenopausal women and in different conditions related to bone loss. In addition, OHC improves pain symptoms and accelerates fracture consolidation in patients with osteopenia or osteoporosis. The ossein-hydroxyapatite complex is significantly more effective in preventing bone loss than calcium carbonate.

Macrophage cell lines derived from major histocompatibility complex II-negative mice

NASA Technical Reports Server (NTRS)

Beharka, A. A.; Armstrong, J. W.; Chapes, S. K.; Spooner, B. S. (Principal Investigator)

1998-01-01

Two bone-marrow-derived macrophage cell lines, C2D and C2Dt, were isolated from major histocompatibility class II negative knock-out mice. The C2D cell line was stabilized by continuous culture in colony-stimulating factor-1 and the C2Dt cell line was transformed with SV40 virus large T antigen. These cells exhibited phenotypic properties of macrophages including morphology and expression of Mac 1 and Mac 2 cell surface molecules. These cells also had comparable growth to the bone-marrow-derived macrophage cell line B6MP102. These new cell lines were not spontaneously cytotoxic and were only capable of modest killing of F5b tumor cells when stimulated with LPS and interferon-gamma, but not when stimulated with LPS alone or with staphylococcal exotoxin. C2D and C2Dt cells phagocytosed labeled Staphylococcus aureus similarly to B6MP102 cells but less well than C2D peritoneal macrophages. These cell lines secreted interleukin-6, but not tumor necrosis factor or nitric oxide in response to LPS or staphlococcal enterotoxins A or B C2D(t) cells were tumorigenic in C2D and C57BL/6J mice but C2D cells were not. These data suggest that macrophage cell lines can be established from bone marrow cells of major histocompatibility complex II-negative mice.

[Effects of nicotine on bone marrow stromal cells proliferation and differentiation of chondrocyte in vitro].

PubMed

Ying, Xiao-zhou; Peng, Lei; Cheng, Shao-wen; Chen, Qing-yu; Zhang, Wei; Kou, Dong-quan; Shen, Yue

2011-11-01

To examine the effects of various concentration of nicotine on bone marrow stromal cells (BMSCs) proliferation and differentiation of cartilaginous in vitro. BMSCs was obtained from femoral bone and tibia of New-Zealand albino rabbit. The cells of the 3rd generation were used in study. Different concentration of nicotine (0, 1 x 10(-7), 1 x 10(-6), 1 x 10(-5) M) were added into BMSCs. BMSCs proliferation was analyzed by MTT assay at the 1, 4, 7, 14 days. The expression of collagen type II and aggrecan as the marker genes of cartilaginous differentiation from BMSCs were detected by reverse transcriptase-polymerase chain reaction (RT-PCR). Microscope showed that BMSCs transformed from round to fusiform shape. The concentration of nicotine in 1 x 10(-7), 1 x 10(-6) M had a significant positive effect on cell proliferation and the expression of type II collagen in a time-dependent manner when supplemented in commonly used induction media (P<0.05). Concentrations of nicotine in 1 x 10(-7) can promote the expression of aggrecan at the 7th day after induction,and in 1 x 10(-5) M may inhibit the expression of type II collagen and aggrecan. It was implied that local application of nicotine at an appropriate concentration may be a promising approach for enhancing cartilaginous differentiation capacity of BMSCs in cartilage tissue engineering.

Effects of Exercise on Bone Status in Female Subjects, from Young Girls to Postmenopausal Women: An Overview of Systematic Reviews and Meta-Analyses.

PubMed

Xu, Jincheng; Lombardi, Giovanni; Jiao, Wei; Banfi, Giuseppe

2016-08-01

Osteoporosis and postmenopausal bone loss pose a huge social and economic burden worldwide. Regular exercise and physical activity are effective interventions for maximizing or maintaining peak bone mass and preventing bone loss in the elderly; however, most recommendations are addressed to the general public and lack specific indications for girls and women, the segment of the population most at risk for developing osteoporosis. The aim of this overview of systematic reviews and meta-analyses was to summarize current evidence for the effects of exercise and physical activity interventions on bone status in girls and women, and to explore whether specific exercise programs exist for improving or maintaining bone mass or bone strength in females. The PubMed, EMBASE, PEDro, and Cochrane Library databases were searched from January 2009, updated to 22 June 2015, using the following groups of search terms: (i) 'physical activity' and 'exercise'; and (ii) 'bone', 'bone health', 'bone strength', 'bone structure', 'bone metabolism', 'bone turnover', and 'bone biomarkers'. Searches and screening were limited to systematic reviews or meta-analyses of studies in females and published in English. Our final analysis included 12 articles that met the inclusion criteria. Combined-impact exercise protocols (impact exercise with resistance training) are the best choice to preserve/improve bone mineral density in pre- and postmenopausal women. Peak bone mass in young girls can be improved with short bouts of school-based high-impact plyometric exercise programs. Whole-body vibration exercises have no beneficial effects on bone in postmenopausal or elderly women. Lifelong exercise, specific for age, is an effective way to sustain bone health in girls and women.

Evaluation of different rotary devices on bone repair in rabbits.

PubMed

Ribeiro Junior, Paulo Domingos; Barleto, Christiane Vespasiano; Ribeiro, Daniel Araki; Matsumoto, Mariza Akemi

2007-01-01

In oral surgery, the quality of bone repair may be influenced by several factors that can increase the morbidity of the procedure. The type of equipment used for ostectomy can directly affect bone healing. The aim of this study was to evaluate bone repair of mandible bone defects prepared in rabbits using three different rotary devices. Fifteen New Zealand rabbits were randomly assigned to 3 groups (n=5) according to type of rotary device used to create bone defects: I--pneumatic low-speed rotation engine, II--pneumatic high-speed rotation engine, and III--electric low-speed rotation engine. The anatomic pieces were surgically obtained after 2, 7 and 30 days and submitted to histological and morphometric analysis. The morphometric results were expressed as the total area of bone remodeling matrix using an image analysis system. Increases in the bone remodeling matrix were noticed with time along the course of the experiment. No statistically significant differences (p>0.05) were observed among the groups at the three sacrificing time points considering the total area of bone mineralized matrix, although the histological analysis showed a slightly advanced bone repair in group III compared to the other two groups. The findings of the present study suggest that the type of rotary device used in oral and maxillofacial surgery does not interfere with the bone repair process.

A predictive radiological analysis of short stems versus both shortened and long stems in primary hip replacement: A case-control study of 100 cases of Metha versus ABG II and Omnifit HA at 2-8years' follow-up.

PubMed

Epinette, J-A; Brax, M; Chammaï, Y

2017-11-01

Short hip stems, intended to conserve bone stock and ensure a more physiological distribution of stress in the femur under loading, are meeting with renewed interest. Radiologic semiology is not known exactly, particularly in relation to conventional implants; we therefore conducted a case-control study of 3 types of implant differing only in stem length: short, shortened or long. The aim was: (1) to compare radiographic aspects, (2) to attempt to systematize medium-term radiologic status for the 3 types, and (3) to assess the impact of radiographic aspect on loosening and revision rates. The short Metha stem is better adapted to the recipient bone than longer stems, without sacrificing stability. A prospective series comprising the first 100 selected cases of hip replacement using the short Metha stem was compared to two other series of 100 "long" (Omnifit HA) and 100 "shortened" (ABG II) stems at comparable follow-up: 4.05±1.44years (range: 2-8years) for Metha, 4.48±0.97years (range: 2-8years) for Omnifit, and 4.75±2.07years (range: 2-8years) for ABG II. Selection criteria in this initial phase were very strict: young age and/or high activity level, with good bone stock and femoral morphology suited to fitting a Metha stem (no "stovepipe" or "champagne-flute" femurs), for which 12.8% of primary hip replacements were selected. Matching was performed by sampling on criteria of age, gender, body-mass index and etiology. Radiographic parameters were compared between the short stem group and the two control groups and classified according to Engh-Massin score (10 points for fixation and 17 for stability). The short Metha stem provided excellent fixation scores: 7.65/10, versus 7.16 (P=0.003) and 5.92 (P=0.0001) for ABG II and Omnifit, respectively. Likewise, stability was scored 14.23/17 for Metha, vs. 14.51 (NS) and 11.83 (P=0.0001) respectively, and the total score was higher for Metha (21.88/27) than ABG II (21.67; P=0.03) or, more particularly, Omnifit (17.83; P=0.0001). The Metha stem was never associated with thigh pain or periprosthetic fracture. 8-year survival was 100%, without significant difference with respect to ABG II (100%; NS) or Omnifit (98.8%; 95% CI: 0.964-1; NS). The apparent radiologic superiority of the short Metha stem requires long-term confirmation in non-selected series. Meanwhile, Metha can be asserted to have demonstrated optimal compromise between lasting bone anchorage and respect of bone physiology under loading at medium term. III, case-control study. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

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

The Role of Crk Adaptor Proteins in Breast Tumorigenesis and Bone Metastasis

DTIC Science & Technology

2012-09-01

purchased from Asterand (Detroit, MI, USA) in 2009 and cultured as in [17] from freeze downs from 2009. Both cell lines under- went standard mouse antibody ...directed muta- genesis using the QuickChange Multi Site-Directed Mutagenesis Kit from Stratagene (La Jolla, CA, USA). Antibodies included: CrkI/II...Ki67, CrkI/II, CrkII or CrkL specific antibodies in high (Grade 3) and low (Grade 1) grade tumors. Images taken using ImageScope; scale bar

Changes in PGE2 signaling after submandibulectomy alter post-tooth extraction socket healing.

PubMed

Mohn, Claudia Ester; Troncoso, Gastón Rodolfo; Bozzini, Clarisa; Conti, María Inés; Fernandez Solari, Javier; Elverdin, Juan Carlos

2018-03-10

Saliva is very important to oral health, and a salivary deficit has been shown to bring serious problems to oral health. There is scant information about the mechanisms through which salivary glands participate in post-tooth extraction socket healing. Therefore, the aim of the present study was to investigate the effect of submandibulectomy (SMx), consisting of the ablation of submandibular and sublingual glands (SMG and SLG, respectively), on PGE 2 signaling and other bone regulatory molecules, such as OPG and RANKL, involved in tooth extraction socket healing. Male Wistar rats, 70 g body weight, were assigned to an experimental (subjected to SMx) or a control group (sham operated). One week later, the animals in both groups underwent bilateral extraction of the first mandibular molars. The effect of SMx on different stages of socket healing after tooth extraction (7, 14, and 30 days) was studied by evaluating some parameters of inflammation, including PGE 2 and its receptors, and of bone metabolism, as well as by performing bone biomechanical studies. SMx increased TNFα and PGE 2 content as well as cyclooxygenase-II (COX-II) expression in tooth socket tissue at almost all the studied time points. SMx also had an effect on mRNA expression of PGE 2 receptors at the different time points, but did not significantly alter osteoprotegerin (OPG) and RANKL mRNA expression at any of the studied time points. In addition, an increase in bone mass density was observed in SMx rats compared with matched controls, and the structural and mechanical bone properties of the mandibular socket bone were also affected by SMx. Our results suggest that the SMG/SLG complex regulates cellular activation and differentiation by modulating the production of molecules intervening in tooth extraction socket repair, including the PGE 2 signaling system, which would therefore account for the higher density and resistance of the newly formed bone in SMx rat. © 2018 by the Wound Healing Society.

The Comparative Efficiency of Four Types of Endodontic Files and Reamers.

DTIC Science & Technology

1981-12-29

an reveree aide Ii neceeary end Identify by block number) Comparative efficiency of endodontic files; endodontic instrumentation ; instrumentation ...sections of bovine bone. Each canal was instrumented to a size 80 using four types of endodontic instruments : Hedstrom S files; K-files; reamers; and the...bovine bone. Each canal was instrumented to a size 80 using four types of endodontic instruments : Hedstrom files; K-files; reamers; and the new Unifile

Texas Emergency Resource Management. Volume II.

DTIC Science & Technology

1979-09-30

direct all users and distributors of sugar and other natural sweeteners in the State to abide by such regulations as may be issued by the U. S. Department...systemic disorders such a, arthritis, heart disease, diabetes or kidney trouble. May treat bone, muscle and joint disorders limits to feet and be kno...dis- orders such as arthritis, heart disease, diabetes or kidney trouble. May treat bone, muscle and joint disorders limited to feet and be known as

An Investigation of Bonding Mechanisms at the Interface of a Prosthetic Material.

DTIC Science & Technology

1977-12-01

II. CONTROLLING OFFICE NAME AND ADDRESS Command — IkThUM eEROFP AGE S Washington, D. C. 20314 144 _______________________ I...which can influence the precipitation of hydroxyapatite in bone. Variable rates of ion release have been achieved by varying (1) Ca/P ratio, (2) the...conducted to establish parameters controlling the bonding of the glass and glass—ceramic materials with bone. These studies have demonstrated that the

Effects of major histocompatibility complex class II knockout on mouse bone mechanical properties during development

NASA Technical Reports Server (NTRS)

Simske, Steven J.; Bateman, Ted A.; Smith, Erin E.; Ferguson, Virginia L.; Chapes, Stephen K.

2002-01-01

We investigated the effect of major histocompatibility complex class II (MHC II) knockout on the development of the mouse peripheral skeleton. These C2D mice had less skeletal development at 8, 12 and 16 weeks of age compared to wild-type C57BL/6J (B6) male mice. The C2D mice had decreased femur mechanical, geometric and compositional measurements compared to wild type mice at each of these ages. C2D femur stiffness (S), peak force in 3-pt bending (Pm), and mineral mass (Min-M) were 74%, 64% and 66%, respectively, of corresponding B6 values at 8 weeks of age. Similar differences were measured at 12 weeks (for which C2D femoral S, Pm and Min-M were 71%, 72% and 73%, respectively, of corresponding B6 values) and at 16 weeks (for which C2D femoral S, Pm and Min-M were 80%, 66% and 61%, respectively, of corresponding B6 values). MHC II knockout delays the development of adult bone properties and is accompanied by lower body mass compared to wild-type controls.

Early inhibitory effects of zoledronic acid in tooth extraction sockets in dogs are negated by recombinant human bone morphogenetic protein.

PubMed

Gerard, David A; Carlson, Eric R; Gotcher, Jack E; Pickett, David O

2014-01-01

This study was conducted with 2 purposes. The first was to determine the effect of a single dose of zoledronic acid (ZA) on the healing of a tooth extraction socket in dogs. The second was to determine if placement of recombinant human bone morphogenetic protein-2 (rhBMP-2)/absorbable collagen sponge (ACS) - INFUSE, (Medtronic, Memphis, TN) into these extraction sockets would inhibit the inhibition on bone healing and remodeling by ZA. Nine adult female beagle dogs (2 to 3 yr old) were placed into 3 groups of 3 dogs each. Group I received 15 mL of sterile saline intravenously; group II received 2.5 mg of ZA intravenously; and group III received 5 mg of ZA intravenously. Forty-five days after treatment, all dogs underwent extraction of noncontiguous right and left mandibular first molars and second premolars. In group I, the right mandibular extraction sockets had nothing placed in them, whereas the left mandibular sockets had only ACS placed in them. In groups II and III, the right mandibular sockets had rhBMP-2/ACS placed in them, whereas the left mandibular sockets had only ACS placed. All extraction sockets were surgically closed. Tetracycline was given intravenously 5 and 12 days later, and all animals were euthanized 15 days after tooth extraction. The extraction sockets and rib and femur samples were harvested immediately after euthanasia, processed, and studied microscopically. A single dose of ZA significantly inhibited healing and bone remodeling in the area of the tooth extractions. The combination of rhBMP-2/ACS appeared to over-ride some of the bone remodeling inhibition of the ZA and increased bone fill in the extraction sites, and remodeling activity in the area was noted. The effects of rhBMP-2/ACS were confined to the area of the extraction sockets because bone activity at distant sites was not influenced. A single dose of ZA administered intravenously inhibits early healing of tooth extraction sockets and bone remodeling in this animal model. The combination of rhBMP-2/ACS significantly increased bone fill and bone remodeling in these areas, negating much of the effect of the ZA. Copyright © 2014 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Three-Dimensional Bio-Printed Scaffold Sleeves With Mesenchymal Stem Cells for Enhancement of Tendon-to-Bone Healing in Anterior Cruciate Ligament Reconstruction Using Soft-Tissue Tendon Graft.

PubMed

Park, Sin Hyung; Choi, Yeong-Jin; Moon, Sang Won; Lee, Byung Hoon; Shim, Jin-Hyung; Cho, Dong-Woo; Wang, Joon Ho

2018-01-01

To investigate the efficacy of the insertion of 3-dimensional (3D) bio-printed scaffold sleeves seeded with mesenchymal stem cells (MSCs) to enhance osteointegration between the tendon and tunnel bone in anterior cruciate ligament (ACL) reconstruction in a rabbit model. Scaffold sleeves were fabricated by 3D bio-printing. Before ACL reconstruction, MSCs were seeded into the scaffold sleeves. ACL reconstruction with hamstring tendon was performed on both legs of 15 adult rabbits (aged 12 weeks). We implanted 15 bone tunnels with scaffold sleeves with MSCs and implanted another 15 bone tunnels with scaffold sleeves without MSCs before passing the graft. The specimens were harvested at 4, 8, and 12 weeks. H&E staining, immunohistochemical staining of type II collagen, and micro-computed tomography of the tunnel cross-sectional area were evaluated. Histologic assessment was conducted with a histologic scoring system. In the histologic assessment, a smooth bone-to-tendon transition through broad fibrocartilage formation was identified in the treatment group, and the interface zone showed abundant type II collagen production on immunohistochemical staining. Bone-tendon healing histologic scores were significantly higher in the treatment group than in the control group at all time points. Micro-computed tomography at 12 weeks showed smaller tibial (control, 9.4 ± 0.9 mm 2 ; treatment, 5.8 ± 2.9 mm 2 ; P = .044) and femoral (control, 9.6 ± 2.9 mm 2 ; treatment, 6.0 ± 1.0 mm 2 ; P = .03) bone-tunnel areas in the treated group than in the control group. The 3D bio-printed scaffold sleeve with MSCs exhibited excellent results in osteointegration enhancement between the tendon and tunnel bone in ACL reconstruction in a rabbit model. If secure biological healing between the tendon graft and tunnel bone can be induced in the early postoperative period, earlier, more successful rehabilitation may be facilitated. Three-dimensional bio-printed scaffold sleeves with MSCs have the potential to accelerate bone-tendon healing in ACL reconstruction. Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Optical assessment of bone bioimplants

NASA Astrophysics Data System (ADS)

Timchenko, P. E.; Timchenko, E. V.; Volova, L. T.; Dolgushkin, D. A.; Boltovskaya, V. V.; Frolov, O. O.; Fedorova, Ya. V.

2017-08-01

The results of application of the Raman spectroscopy method for the estimation of alternative sources for the production of bone spongy implants using the "Lioplast" technology, namely, the femoral heads resected in the operation of hip replacement surgery, are presented. It is shown that Raman spectroscopy can be used to estimate the component composition of the surface of bone implants during their processing. Comparing different sources of sponge bone production, no significant differences were found, but there are differences in the ratio of the intensities of the Raman peaks at wave numbers 1555 cm-1 and 1665 cm-1 corresponding to amide II and amide I, and also in the intensity of Raman peaks at wave numbers of 959 cm-1 (PO4 3- (ν1)) and 1068 cm-1 (CO3 2- (ν1) B-type substitution).

Reduced functional loads alter the physical characteristics of the bone-periodontal ligament-cementum complex.

PubMed

Niver, E L; Leong, N; Greene, J; Curtis, D; Ryder, M I; Ho, S P

2011-12-01

Adaptive properties of the bone-periodontal ligament-tooth complex have been identified by changing the magnitude of functional loads using small-scale animal models, such as rodents. Reported adaptive responses as a result of lower loads due to softer diet include decreased muscle development, change in structure-function relationship of the cranium, narrowed periodontal ligament space, and changes in the mineral level of the cortical bone and alveolar jaw bone and in the glycosaminoglycans of the alveolar bone. However, the adaptive role of the dynamic bone-periodontal ligament-cementum complex to prolonged reduced loads has not been fully explained to date, especially with regard to concurrent adaptations of bone, periodontal ligament and cementum. Therefore, in the present study, using a rat model, the temporal effect of reduced functional loads on physical characteristics, such as morphology and mechanical properties and the mineral profiles of the bone-periodontal ligament-cementum complex was investigated. Two groups of 6-wk-old male Sprague-Dawley rats were fed nutritionally identical food with a stiffness range of 127-158 N/mm for hard pellet or 0.3-0.5 N/mm for soft powder forms. Spatio-temporal adaptation of the bone-periodontal ligament-cementum complex was identified by mapping changes in the following: (i) periodontal ligament collagen orientation and birefringence using polarized light microscopy, bone and cementum adaptation using histochemistry, and bone and cementum morphology using micro-X-ray computed tomography; (ii) mineral profiles of the periodontal ligament-cementum and periodontal ligament-bone interfaces by X-ray attenuation; and (iii) microhardness of bone and cementum by microindentation of specimens at ages 6, 8, 12 and 15 wk. Reduced functional loads over prolonged time resulted in the following adaptations: (i) altered periodontal ligament orientation and decreased periodontal ligament collagen birefringence, indicating decreased periodontal ligament turnover rate and decreased apical cementum resorption; (ii) a gradual increase in X-ray attenuation, owing to mineral differences, at the periodontal ligament-bone and periodontal ligament-cementum interfaces, without significant differences in the gradients for either group; (iii) significantly (p < 0.05) lower microhardness of alveolar bone (0.93 ± 0.16 GPa) and secondary cementum (0.803 ± 0.13 GPa) compared with the higher load group insert bone = (1.10 ± 0.17 and cementum = 0.940 ± 0.15 GPa, respectively) at 15 wk, indicating a temporal effect of loads on the local mineralization of bone and cementum. Based on the results from this study, the effect of reduced functional loads for a prolonged time could differentially affect morphology, mechanical properties and mineral variations of the local load-bearing sites in the bone-periodontal ligament-cementum complex. These observed local changes in turn could help to explain the overall biomechanical function and adaptations of the tooth-bone joint. From a clinical translation perspective, our study provides an insight into modulation of load on the complex for improved tooth function during periodontal disease and/or orthodontic and prosthodontic treatments. © 2011 John Wiley & Sons A/S.

Management of localized advance loss of periodontal support associated Grade II furcation and intrabony defect in chronic periodontitis patient through amalgamation of platelet-rich fibrin and hydroxyapatite bioactive glass composite granules.

PubMed

Salaria, Sanjeev Kumar; Ghuman, Simrat Kaur; Kumar, Saurabh; Sharma, Garima

2016-01-01

Periodontal disease is infectious, complex, multifactorial, chronic inflammatory disease of supporting periodontal tissues that not only alters the bone morphology but also leads to the reduction in bone height. Different types of bony deformities such as horizontal, vertical, craters, and furcation result from periodontal disease, but vertical and Grade II furcation defects are more amenable to regenerative periodontal therapy. The present case report describes the current concept of periodontal diagnosis and the clinical radiographical efficiency of platelet-rich fibrin and hydroxyapatite bioactive glass composite granules graft combination in the management of localized advance osseous defects with respect to tooth number 36 in chronic periodontitis patient at 1 year postoperatively.

Rigid external maxillary distraction and rhinoplasty for pyknodysostosis.

PubMed

Varol, Altan; Sabuncuoglu, Fidan Alakus; Sencimen, Metin; Akcam, Timur; Olmez, Hüseyin; Basa, Selçuk

2011-05-01

This article reports the treatment of an 33-year-old female patient with pyknodysostosis by rigid external distraction II midface distraction system. The patient with pyknodysostosis described in this report had severe midfacial hypoplasia. Correction of this by use of routine orthognathic surgery would require osteosynthesis and bone grafting. Risk of infection and/or nonunion after such a surgical procedure was considered too great, and therefore the possibility of treatment by distraction osteogenesis of the maxilla was evaluated. The rigid external distraction II midface distraction system was used to relocate the hypoplastic maxilla at anterior-inferior projection. Distraction osteogenesis should be considered as the primary reconstructive method for maxillofacial deformities in patients with sclerosing bone dysplasias, since this is the second reported case treated successfully with rigid external distraction.

Adsorption/reduction of Hg(II) and Pb(II) from aqueous solutions by using bone ash/nZVI composite: effects of aging time, Fe loading quantity and co-existing ions.

PubMed

Gil, Antonio; Amiri, Mohammad Javad; Abedi-Koupai, Jahangir; Eslamian, Saeid

2018-01-01

In this research, a versatile and highly efficient method for the stabilization of nanoscale zerovalent iron particles (nZVI) on the surface of ostrich bone ash (OBA) was presented as a novel inorganic adsorbent (OBA/nZVI) for the removal of Hg(II) and Pb(II) ions from aqueous solutions, even after 1 year of storage under room conditions. The removal behavior of the OBA/nZVI was assessed as a function of the initial pH, contact time, initial pollutants concentration, temperature, amount of adsorbent, effect of competitive metal ions, and ionic strength. The synthesized adsorbent was characterized by several techniques including N 2 adsorption at - 196 °C, FT-IR spectroscopy, scanning electron microscopy, X-ray diffraction, and zeta potential. The results confirmed that the OBA is a good candidate as support of nZVI. The maxima adsorption capacity for Hg(II) and Pb(II) ions found from experimental results were 170 and 160 mg g -1 , when the loading quantities of Fe were 20%. The equilibrium sorption data obeyed a Langmuir-Freundlich isotherm type model. The kinetic data of the adsorption followed the mechanism of the pseudo-second-order model. The thermodynamic experiments indicated that the removal of metal ions were feasible, endothermic, and spontaneous. It can be found that fresh and aged OBA/nZVI maintained its usability even after five cycles in the order: fresh (OBA/nZVI)-Hg(II) > fresh (OBA/nZVI)-Pb(II) > aged (OBA/nZVI)-Hg(II) > aged (OBA/nZVI)-Pb(II), which indicate that OBA/nZVI can be regenerated as adsorbent. The existence of Fe in the OBA/nZVI was proved by SEM-EDX results and X-ray diffraction analysis also confirmed adsorption/reduction of some of the Hg(II) to Hg 0 and Pb(II) to Pb 0 .

Regulatory elements driving the expression of skeletal lineage reporters differ during bone development and adulthood.

PubMed

Stiers, Pieter-Jan; van Gastel, Nick; Moermans, Karen; Stockmans, Ingrid; Carmeliet, Geert

2017-12-01

To improve bone healing or regeneration more insight in the fate and role of the different skeletal cell types is required. Mouse models for fate mapping and lineage tracing of skeletal cells, using stage-specific promoters, have advanced our understanding of bone development, a process that is largely recapitulated during bone repair. However, validation of these models is often only performed during development, whereas proof of the activity and specificity of the used promoters during the bone regenerative process is limited. Here, we show that the regulatory elements of the 6kb collagen type II promoter are not adequate to drive gene expression during bone repair. Similarly, the 2.3kb promoter of collagen type I lacks activity in adult mice, but the 3.2kb promoter is suitable. Furthermore, Cre-mediated fate mapping allows the visualization of progeny, but this label retention may hinder to distinguish these cells from ones with active expression of the marker at later time points. Together, our results show that the lineage-specific regulatory elements driving gene expression during bone development differ from those required later in life and during bone repair, and justify validation of lineage-specific cell tracing and gene silencing strategies during fracture healing and bone regenerative applications. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparative study of new bone formation capability of zirconia bone graft material in rabbit calvarial.

PubMed

Kim, Ik-Jung; Shin, Soo-Yeon

2018-06-01

The purpose of this study was to compare the new bone formation capability of zirconia with those of other synthetic bone grafts. Twelve rabbits were used and four 6-mm diameter transcortical defects were formed on each calvaria. Each defect was filled with Osteon II (Os), Tigran PTG (Ti), and zirconia (Zi) bone grafts. For the control group, the defects were left unfilled. The rabbits were sacrificed at 2, 4, and 8 weeks. Specimens were analyzed through micro computed tomography (CT) and histomorphometric analysis. The Ti and Zi groups showed significant differences in the amount of newly formed bone between 2 and 4 weeks and between 2 and 8 weeks ( P <.05). The measurements of total bone using micro CT showed significant differences between the Os and Ti groups and between the Os and Zi groups at 2 and 8 weeks ( P <.05). Comparing by week in each group, the Ti group showed a significant difference between 4 and 8 weeks. Histomorphometric analysis also showed significant differences in new bone formation between the control group and the experimental groups at 2, 4, and 8 weeks ( P <.05). In the comparison of newly formed bone, significant differences were observed between 2 and 4 weeks and between 2 and 8 weeks ( P <.05) in all groups. Zirconia bone graft material showed satisfactory results in new bone formation and zirconia could be used as a new synthetic bone graft material.

Weak bones in diabetes mellitus - an update on pharmaceutical treatment options.

PubMed

Lin, Daphne P L; Dass, Crispin R

2018-01-01

Diabetes mellitus is often associated with a number of complications such as nephropathy, neuropathy, retinopathy and foot ulcers. However, weak bone is a diabetic complication that is often overlooked. Although the exact mechanism for weak bones within diabetes mellitus is unclear, studies have shown that the mechanism does differ in both type I (T1DM) and type II diabetes (T2DM). This review, however, investigates the application of mesenchymal stem cells, recombinant human bone morphogenetic protein-2, teriparatide, insulin administration and the effectiveness of a peroxisome proliferator-activated receptor-ϒ modulator, netoglitazone in the context of diabetic weak bones. In T1DM, weak bones may be the result of defective osteoblast activity, the absence of insulin's anabolic effects on bone, the deregulation of the bone-pancreas negative feedback loop and advanced glycation end product (AGE) aggregation within the bone matrix as a result of hyperglycaemia. Interestingly, T2DM patients placed on insulin administration, thiazolidinediones, SGLT2 inhibitors and sulfonylureas have an associated increased fracture risk. T2DM patients are also observed to have high sclerostin levels that impair osteoblast gene transcription, AGE aggregation within bone, which compromises bone strength and a decrease in esRAGE concentration resulting in a negative association with vertebral fractures. Effective treatment options for weak bones in the context of diabetes are currently lacking. There is certainly scope for discovery and development of novel agents that could alleviate this complication in diabetes patients. © 2017 Royal Pharmaceutical Society.

The prevalence of the sesamoid bones of the hand: a systematic review and meta-analysis.

PubMed

Yammine, Kaissar

2014-11-01

The literature contains various estimates of the prevalence and distribution of the sesamoid bones in the hands. The aims of this systematic review are to provide a better estimate of the frequency of hand sesamoids and its association with variables such as ancestry, gender, and side. Nineteen studies met the inclusion criteria. The pooled rates of the sensitive meta-analyses from large-sample studies in adults showed: (a) true overall rates of 99.9% for the metacarpophalangeal (MCP) joint of the thumb (MCP-I), 53% for the interphalangeal joint (IP-I), 43.4% for the MCP of the index (MCP-II), 1.47% for the MCP of the medius finger (MCP-III), 0.6% for the MCP of the ring finger (MCP-IV), and 67.7% for the MCP of the auricular finger (MCP-V); (b) true radiological rates of 99.9% for the radial thumb sesamoid, 99.6% for the ulnar thumb sesamoid, 47.8% for IP-I, 40% for MCP-II, 1.3% for MCP-III, 0.8% for MCP-VI, and 62.8% for MCP-V. Black, Middle Eastern, and European ancestries conferred significantly higher sesamoid frequencies at IP-I, MCP-II, and MCP-V, respectively. There was a significant association with female gender at MCP-II, MCP-IV, and MCP-V, with ORs of 1.53, 4, and 1.3, respectively, and a nonsignificant "female" trend for the other locations. There was no significant association with hand side. The pooled rates of hand sesamoids in children aged 10-17 years were 92.7, 42.2, 33.8, 0.5, 0.3, and 36.5% for MCP-I, IP-I, MCP-II, MCP-III, MCP-IV, and MCP-V, respectively. The findings of this evidence-based anatomical review provide quantitative evidence that the incidence of sesamoid bones in human hands depends on genetic rather than functional factors. © 2014 Wiley Periodicals, Inc.

Effects of in vivo static compressive loading on aggrecan and type II and X collagens in the rat growth plate extracellular matrix.

PubMed

Cancel, Mathilde; Grimard, Guy; Thuillard-Crisinel, Delphine; Moldovan, Florina; Villemure, Isabelle

2009-02-01

Mechanical loads are essential to normal bone growth, but excessive loads can lead to progressive deformities. In addition, growth plate extracellular matrix remodelling is essential to regulate the normal longitudinal bone growth process and to ensure physiological bone mineralization. In order to investigate the effects of static compression on growth plate extracellular matrix using an in vivo animal model, a loading device was used to precisely apply a compressive stress of 0.2 MPa for two weeks on the seventh caudal vertebra (Cd7) of rats during the pubertal growth spurt. Control, sham and loaded groups were studied. Growth modulation was quantified based on calcein labelling, and three matrix components (type II and X collagens, and aggrecan) were assessed using immunohistochemistry/safranin-O staining. As well, extracellular matrix components and enzymes (MMP-3 and -13, ADAMTS-4 and -5) were studied by qRT-PCR. Loading reduced Cd7 growth by 29% (p<0.05) and 15% (p=0.07) when compared to controls and shams respectively. No significant change could be observed in the mRNA expression of collagens and the proteolytic enzyme MMP-13. However, MMP-3 was significantly increased in the loaded group as compared to the control group (p<0.05). No change was observed in aggrecan and ADAMTS-4 and -5 expression. Low immunostaining for type II and X collagens was observed in 83% of the loaded rats as compared to the control rats. This in vivo study shows that, during pubertal growth spurt, two-week static compression reduced caudal vertebrae growth rates; this mechanical growth modulation occurred with decreased type II and X collagen proteins in the growth plate.

The influence of micro and macro-geometry in term of bone-implant interface in two implant systems: an histomorphometrical study

PubMed Central

ROCCI, A.; CALCATERRA, R.; DI GIROLAMO, M.; ROCCI, M.; ROCCI, C.; BAGGI, L.

2015-01-01

SUMMARY Objective Many factors could affect the osseous healing of implants such as surface topography of biomaterial, the status of the bone/implant site, implant loading conditions, surgical technique and implant design. The aim of this study was to analyze the BIC of 2 different implants systems characterized by different micro and macrogeometry, that were placed in the posterior maxillary and mandibular jaws of humans, clinically unloaded and retrieved for histomorphometric analyses after 12 weeks. Material and method The patients were divided in two groups (Group I and II); group I was composed by 4 patients that each received in the posterior areas of mandible one type A implant [GTB-Plan1Health Amaro (UD) Italy] one type B implant (OsseoSpeed Astra Tech, Dentsply Molndal, Sweden). Group II was composed by 3 patients that each received in the posterior areas of jawsbone one type A implant [GTB-Plan1Health Amaro (UD) Italy] one type B implant (OsseoSpeed Astra Tech, Dentsply Molndal, Sweden). After 12 weeks of healing all the implants of both groups were harvested with the peri-implant bone tissues. Osseointegration process was evaluated throughout measurements of BIC. Results No statistical significance differences were found among the mean percentage of BIC of Group I – type A were 66,51% versus 49,96% in Group I – type B, as well as among the mean percentage of BIC of Group II – type A were 43.7% versus 60.02% in Group II – type B. Conclusions Our results highlight that the mean percentage of BIC after 12 weeks from the implants placement without functional loading is not influenced by the composition of the implant surface. PMID:28042421

The influence of micro and macro-geometry in term of bone-implant interface in two implant systems: an histomorphometrical study.

PubMed

Rocci, A; Calcaterra, R; DI Girolamo, M; Rocci, M; Rocci, C; Baggi, L

2015-01-01

Many factors could affect the osseous healing of implants such as surface topography of biomaterial, the status of the bone/implant site, implant loading conditions, surgical technique and implant design. The aim of this study was to analyze the BIC of 2 different implants systems characterized by different micro and macrogeometry, that were placed in the posterior maxillary and mandibular jaws of humans, clinically unloaded and retrieved for histomorphometric analyses after 12 weeks. The patients were divided in two groups (Group I and II); group I was composed by 4 patients that each received in the posterior areas of mandible one type A implant [GTB-Plan1Health Amaro (UD) Italy] one type B implant (OsseoSpeed Astra Tech, Dentsply Molndal, Sweden). Group II was composed by 3 patients that each received in the posterior areas of jawsbone one type A implant [GTB-Plan1Health Amaro (UD) Italy] one type B implant (OsseoSpeed Astra Tech, Dentsply Molndal, Sweden). After 12 weeks of healing all the implants of both groups were harvested with the peri-implant bone tissues. Osseointegration process was evaluated throughout measurements of BIC. No statistical significance differences were found among the mean percentage of BIC of Group I - type A were 66,51% versus 49,96% in Group I - type B, as well as among the mean percentage of BIC of Group II - type A were 43.7% versus 60.02% in Group II - type B. Our results highlight that the mean percentage of BIC after 12 weeks from the implants placement without functional loading is not influenced by the composition of the implant surface.

In vitro study of electrodeposited fluoridated hydroxyapatite coating on G-II titanium with a nanostructured TiO2 interlayer.

PubMed

Lin, Jin-Shyong; Tsai, Tzung-Bau; Say, Wen-Ching; Chiu, Chun; Chen, Shih-Hsun

2017-04-04

Titanium and its alloys have been widely used as orthopedic and dental implants for several decades due to their superior mechanical properties, corrosion resistance and biocompatibility. Recently, many researches revealed that the hydroxyapatite coatings on biomedical materials can further improve their biocompatibility and bioactivity. However, hydroxyapatite coatings are easily decomposed, weakening the bonding between implants and bone tissues and resulting in a high dissolution rate in the biological environment. Prolonging the lifetime of hydroxyapatite in implants is valuable for improving postoperative quality. Hydroxyapatite is the primary inorganic component of bones and teeth. A suitable amount of fluoride ions would be beneficial for the formation of fluoridated hydroxyapatite, which can enhance bone-cell response and the acid resistance of enamel. In this study, G-II titanium substrate was anodized to form a TiO 2 interlayer with a nanotube structure. An electrolyte composed of fluoride, calcium and phosphorus ions was prepared for electroplating fluoridated hydroxyapatite (FHA) coatings onto anodized G-II titanium substrates at a constant voltage. The obtained coatings were examined for their microstructure, mechanical properties; moreover, the changes of apatite structure, surface morphology and corrosion resistance were further investigated after immersion in simulated body fluid (SBF) for a number of weeks. The results show that FHA coatings have a higher surface roughness and hardness than plain hydroxyapatite. After immersion in SBF, the FHA coatings induced the nucleation and growth of apatite on the surface and increased their crystallinity. In a potentiodynamic polarization test, FHA coatings exhibited a better anti-corrosion ability than bare G-II titanium substrate in SBF. Additionally, the anodized TiO 2 nanotube improved the adhesion and corrosion resistance of FHA as well.

Evaluation of ERα and VDR gene polymorphisms in relation to bone mineral density in Turkish postmenopausal women.

PubMed

Kurt, Ozlem; Yilmaz-Aydogan, Hulya; Uyar, Mehmet; Isbir, Turgay; Seyhan, Mehmet Fatih; Can, Ayse

2012-06-01

It has been suggested that the estrogen receptor alpha (ERα) and vitamin D receptor (VDR) genes as possibly implicated in reduced bone mineral density (BMD) in osteoporosis. The present study investigated the relation of ERα PvuII/XbaI polymorphisms and VDR FokI/TaqI polymorphisms with BMD in Turkish postmenopausal women. Eighty-one osteoporotic and 122 osteopenic postmenopausal women were recruited. For detection of the polymorphisms, polymerase chain reaction-restriction fragment lenght polymorphism techniques have been used. BMD was measured at the lumbar spine and hip by dual-energy X-ray absorptiometry. Distributions of ERα (PvuII dbSNP: rs2234693, XbaI dbSNP: rs9340799) and VDR genotypes (FokI dbSNP rs10735810, TaqI dbSNP: rs731236) were similar in study population. Although overall prevalence of osteoporosis had no association with these genotypes, the prevalence of decreased femoral neck BMD values were higher in the subjects with ERα PvuII "PP" and ERα XbaI "XX" genotypes than in those with "Pp/pp" genotypes and "xx" genotype, respectively (P < 0.05). Furthermore, subjects with VDR FokI "FF" genotype had lower BMD values of femoral neck and total hip compared to those with "Ff" genotype (P < 0.05). In the logistic regression analysis, we confirmed the presence of relationships between the VDR FokI "FF" genotypes, BMI ≤ 27.5, age ≥ 55 and the increased risk of femoral neck BMD below 0.8 value in postmenopausal women. The present data suggests that the ERα PvuII/XbaI and VDR FokI polymorphisms may contribute to the determination of bone mineral density in Turkish postmenopausal women.

Does microvascularization of the footprint play a role in rotator cuff healing of the shoulder?

PubMed

Bonnevialle, Nicolas; Bayle, Xavier; Faruch, Marie; Wargny, Matthieu; Gomez-Brouchet, Anne; Mansat, Pierre

2015-08-01

The aim of the study was to evaluate the relationship between bone microvascularization of the footprint and tendon integrity after rotator cuff repair of the shoulder. Forty-eight patients (mean age, 59 years; ±7.9) with a chronic rotator cuff tear underwent a tendon repair with a single-row technique and were studied prospectively. A core obtained from the footprint during the procedure allowed determination of the bone's microvascularization with an immunohistochemistry technique using anti-CD34 antibodies. Clinical evaluation was performed at a minimum of 12-month follow-up, and rotator cuff integrity was assessed with ultrasound according to Sugaya's classification. At a mean follow-up of 13 months, the Constant score improved from 40 to 75 points; American Shoulder and Elbow Surgeons score, from 59 to 89 points; and subjective shoulder value, from 38% to 83% (P < .001). Ultrasound identified 18 patients with Sugaya type I healing, 27 patients with type II, and 3 patients with type IV. No patients showed Sugaya type III or V repairs. The rate of microvascularization of the footprint was 15.6%, 13.9%, and 4.2% for type I, II, and IV tendon integrity, respectively (I vs. II, P = .22; II vs. IV, P = .02; I vs. IV, P = .0022). Patients with a history of corticosteroid injection had a lower rate of microvascularization than the others (10.3% vs. 16.2%; P = .03). Even if overall satisfactory clinical outcomes are achieved after a rotator cuff repair, bone microvascularization of the footprint plays a role in rotator cuff healing. A lower rate of microvessels decreases the tendon integrity and healing potential after repair. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Disruption of Annexin II /p11 Interaction Suppresses Leukemia Cell Binding, Homing and Engraftment, and Sensitizes the Leukemia Cells to Chemotherapy.

PubMed

Gopalakrishnapillai, Anilkumar; Kolb, E Anders; Dhanan, Priyanka; Mason, Robert W; Napper, Andrew; Barwe, Sonali P

2015-01-01

The bone marrow microenvironment plays an important role in acute lymphoblastic leukemia (ALL) cell proliferation, maintenance, and resistance to chemotherapy. Annexin II (ANX2) is abundantly expressed on bone marrow cells and complexes with p11 to form ANX2/p11-hetero-tetramer (ANX2T). We present evidence that p11 is upregulated in refractory ALL cell lines and patient samples. A small molecule inhibitor that disrupts ANX2/p11 interaction (ANX2T inhibitor), an anti-ANX2 antibody, and knockdown of p11, abrogated ALL cell adhesion to osteoblasts, indicating that ANX2/p11 interaction facilitates binding and retention of ALL cells in the bone marrow. Furthermore, ANX2T inhibitor increased the sensitivity of primary ALL cells co-cultured with osteoblasts to dexamethasone and vincristine induced cell death. Finally, in an orthotopic leukemia xenograft mouse model, the number of ALL cells homing to the bone marrow was reduced by 40-50% in mice injected with anti-ANX2 antibody, anti-p11 antibody or ANX2T inhibitor compared to respective controls. In a long-term engraftment assay, the percentage of ALL cells in mouse blood, bone marrow and spleen was reduced in mice treated with agents that disrupt ANX2/p11 interaction. These data show that disruption of ANX2/p11 interaction results in reduced ALL cell adhesion to osteoblasts, increased ALL cell sensitization to chemotherapy, and suppression of ALL cell homing and engraftment.

Effects of whole-body vibration training on physical function, bone and muscle mass in adolescents and young adults with cerebral palsy.

PubMed

Gusso, Silmara; Munns, Craig F; Colle, Patrícia; Derraik, José G B; Biggs, Janene B; Cutfield, Wayne S; Hofman, Paul L

2016-03-03

We performed a clinical trial on the effects of whole-body vibration training (WBVT) on muscle function and bone health of adolescents and young adults with cerebral palsy. Forty participants (11.3-20.8 years) with mild to moderate cerebral palsy (GMFCS II-III) underwent 20-week WBVT on a vibration plate for 9 minutes/day 4 times/week at 20 Hz (without controls). Assessments included 6-minute walk test, whole-body DXA, lower leg pQCT scans, and muscle function (force plate). Twenty weeks of WBVT were associated with increased lean mass in the total body (+770 g; p = 0.0003), trunk (+410 g; p = 0.004), and lower limbs (+240 g; p = 0.012). Bone mineral content increased in total body (+48 g; p = 0.0001), lumbar spine (+2.7 g; p = 0.0003), and lower limbs (+13 g; p < 0.0001). Similarly, bone mineral density increased in total body (+0.008 g/cm(2); p = 0.013), lumbar spine (+0.014 g/cm(2); p = 0.003), and lower limbs (+0.023 g/cm(2); p < 0.0001). Participants reduced the time taken to perform the chair test, and improved the distance walked in the 6-minute walk test by 11% and 35% for those with GMFCS II and III, respectively. WBVT was associated with increases in muscle mass and bone mass and density, and improved mobility of adolescents and young adults with cerebral palsy.

Robotic-arm assisted total hip arthroplasty results in smaller acetabular cup size in relation to the femoral head size: a matched-pair controlled study.

PubMed

Suarez-Ahedo, Carlos; Gui, Chengcheng; Martin, Timothy J; Chandrasekaran, Sivashankar; Lodhia, Parth; Domb, Benjamin G

2017-03-31

To compare the acetabular component size relative to the patient's native femoral head size between conventional THA (CTHA) approach and robotic-arm assisted THA (RTHA) to infer which of these techniques preserved more acetabular bone. Patients were included if they had primary osteoarthritis (OA) and underwent total hip replacement between June 2008 and March 2014. Patients were excluded if they had missing or rotated postoperative anteroposterior radiographs. RTHA patients were matched to a control group of CTHA patients, in terms of preoperative native femoral head size, age, gender, body mass index (BMI) and approach. Acetabular cup size relative to femoral head size was used as a surrogate for amount of bone resected. We compared the groups according to 2 measures describing acetabular cup diameter (c) in relation to femoral head diameter (f): (i) c-f, the difference between cup diameter and femoral head diameter and (ii) (c-f)/f, the same difference as a fraction of femoral head diameter. 57 matched pairs were included in each group. There were no significant differences between groups for demographic measures, femoral head diameter, or acetabular cup diameter (p>0.05). However, measures (i) and (ii) did differ significantly between the groups, with lower values in the RTHA group (p<0.02). Using acetabular cup size relative to femoral head size as an approximate surrogate measure of acetabular bone resection may suggest greater preservation of bone stock using RTHA compared to CTHA. Further studies are needed to validate the relationship between acetabular cup size and bone loss in THA.

Two-time scale fatigue modelling: application to damage

NASA Astrophysics Data System (ADS)

Devulder, Anne; Aubry, Denis; Puel, Guillaume

2010-05-01

A temporal multiscale modelling applied to fatigue damage evolution in cortical bone is presented. Microdamage accumulation in cortical bone, ensued from daily activities, leads to impaired mechanical properties, in particular by reducing the bone stiffness and inducing fatigue. However, bone damage is also known as a stimulus to bone remodelling, whose aim is to repair and generate new bone, adapted to its environment. This biological process by removing fatigue damage seems essential to the skeleton lifetime. As daily activities induce high frequency cycles (about 10,000 cycles a day), identifying two-time scale is very fruitful: a fast one connected with the high frequency cyclic loading and a slow one related to a quasi-static loading. A scaling parameter is defined between the intrinsic time (bone lifetime of several years) and the high frequency loading (few seconds). An asymptotic approach allows to decouple the two scales and to take into account history effects (Guennouni and Aubry in CR Acad Sci Paris Ser II 20:1765-1767, 1986). The method is here applied to a simple case of fatigue damage and a real cortical bone microstructure. A significant reduction in the amount of computation time in addition to a small computational error between time homogenized and non homogenized models are obtained. This method seems thus to give new perspectives to assess fatigue damage and, with regard to bone, to give a better understanding of bone remodelling.

Trapezium Bone Density-A Comparison of Measurements by DXA and CT.

PubMed

Breddam Mosegaard, Sebastian; Breddam Mosegaard, Kamille; Bouteldja, Nadia; Bæk Hansen, Torben; Stilling, Maiken

2018-01-18

Bone density may influence the primary fixation of cementless implants, and poor bone density may increase the risk of implant failure. Before deciding on using total joint replacement as treatment in osteoarthritis of the trapeziometacarpal joint, it is valuable to determine the trapezium bone density. The aim of this study was to: (1) determine the correlation between measurements of bone mineral density of the trapezium obtained by dual-energy X-ray absorptiometry (DXA) scans by a circumference method and a new inner-ellipse method; and (2) to compare those to measurements of bone density obtained by computerized tomography (CT)-scans in Hounsfield units (HU). We included 71 hands from 59 patients with a mean age of 59 years (43-77). All patients had Eaton-Glickel stage II-IV trapeziometacarpal (TM) joint osteoarthritis, were under evaluation for trapeziometacarpal total joint replacement, and underwent DXA and CT wrist scans. There was an excellent correlation (r = 0.94) between DXA bone mineral density measures using the circumference and the inner-ellipse method. There was a moderate correlation between bone density measures obtained by DXA- and CT-scans with (r = 0.49) for the circumference method, and (r = 0.55) for the inner-ellipse method. DXA may be used in pre-operative evaluation of the trapezium bone quality, and the simpler DXA inner-ellipse measurement method can replace the DXA circumference method in estimation of bone density of the trapezium.

Angiotensin II Infusion Induces Marked Diaphragmatic Skeletal Muscle Atrophy

PubMed Central

Rezk, Bashir M.; Yoshida, Tadashi; Semprun-Prieto, Laura; Higashi, Yusuke; Sukhanov, Sergiy; Delafontaine, Patrice

2012-01-01

Advanced congestive heart failure (CHF) and chronic kidney disease (CKD) are characterized by increased angiotensin II (Ang II) levels and are often accompanied by significant skeletal muscle wasting that negatively impacts mortality and morbidity. Both CHF and CKD patients have respiratory muscle dysfunction, however the potential effects of Ang II on respiratory muscles are unknown. We investigated the effects of Ang II on diaphragm muscle in FVB mice. Ang II induced significant diaphragm muscle wasting (18.7±1.6% decrease in weight at one week) and reduction in fiber cross-sectional area. Expression of the E3 ubiquitin ligases atrogin-1 and muscle ring finger-1 (MuRF-1) and of the pro-apoptotic factor BAX was increased after 24 h of Ang II infusion (4.4±0.3 fold, 3.1±0.5 fold and 1.6±0.2 fold, respectively, compared to sham infused control) suggesting increased muscle protein degradation and apoptosis. In Ang II infused animals, there was significant regeneration of injured diaphragm muscles at 7 days as indicated by an increase in the number of myofibers with centralized nuclei and high expression of embryonic myosin heavy chain (E-MyHC, 11.2±3.3 fold increase) and of the satellite cell marker M-cadherin (59.2±22.2% increase). Furthermore, there was an increase in expression of insulin-like growth factor-1 (IGF-1, 1.8±0.3 fold increase) in Ang II infused diaphragm, suggesting the involvement of IGF-1 in diaphragm muscle regeneration. Bone-marrow transplantation experiments indicated that although there was recruitment of bone-marrow derived cells to the injured diaphragm in Ang II infused mice (267.0±74.6% increase), those cells did not express markers of muscle stem cells or regenerating myofibers. In conclusion, Ang II causes marked diaphragm muscle wasting, which may be important for the pathophysiology of respiratory muscle dysfunction and cachexia in conditions such as CHF and CKD. PMID:22276172

Antitumor effect and toxicity of free rhodium (II) citrate and rhodium (II) citrate-loaded maghemite nanoparticles in mice bearing breast cancer.

PubMed

Carneiro, Marcella Lemos Brettas; Peixoto, Raphael C A; Joanitti, Graziela A; Oliveira, Ricardo G S; Telles, Luis A M; Miranda-Vilela, Ana L; Bocca, Anamélia L; Vianna, Leonora M S; da Silva, Izabel C R; de Souza, Aparecido R; Lacava, Zulmira G M; Báo, Sônia N

2013-02-16

Magnetic fluids containing superparamagnetic iron oxide nanoparticles represent an attractive platform as nanocarriers in chemotherapy. Recently, we developed a formulation of maghemite nanoparticles coated with rhodium (II) citrate, which resulted in in vitro cytotoxicity enhanced up to 4.6 times when compared to free rhodium (II) citrate formulation on breast carcinoma cells. In this work, we evaluate the antitumor activity and toxicity induced by these formulations in Balb/c mice bearing orthotopic 4T1 breast carcinoma. Mice were evaluated with regard to the treatments' toxicity through analyses of hemogram, serum levels of alanine aminotransferase, iron, and creatinine; DNA fragmentation and cell cycle of bone marrow cells; and liver, kidney and lung histology. In addition, the antitumor activity of rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate was verified by tumor volume reduction, histology and immunohistochemistry. Regarding the treatments' toxicity, no experimental groups had alterations in levels of serum ALT or creatinine, and this suggestion was corroborated by the histopathologic examination of liver and kidney of mice. Moreover, DNA fragmentation frequency of bone marrow cells was lower than 15% in all experimental groups. On the other hand, the complexes rhodium (II) citrate-functionalized maghemite and free rhodium (II) citrate led to a marked growth inhibition of tumor and decrease in CD31 and Ki-67 staining. In summary, we demonstrated that both rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate formulations exhibited antitumor effects against 4T1 metastatic breast cancer cell line following intratumoral administration. This antitumor effect was followed by inhibition of both cell proliferation and microvascularization and by tumor tissue injury characterized as necrosis and fibrosis. Remarkably, this is the first published report demonstrating the therapeutic efficacy of maghemite nanoparticles coated with rhodium (II) citrate. This treatment prolonged the survival period of treated mice without inducing apparent systemic toxicity, which strengthens its use for future breast cancer therapeutic applications.

Stem cell niches and other factors that influence the sensitivity of bone marrow to radiation-induced bone cancer and leukaemia in children and adults

PubMed Central

Richardson, Richard B

2011-01-01

Purpose: This paper reviews and reassesses the internationally accepted niches or ‘targets’ in bone marrow that are sensitive to the induction of leukaemia and primary bone cancer by radiation. Conclusions: The hypoxic conditions of the 10 μm thick endosteal/osteoblastic niche where preleukemic stem cells and hematopoietic stem cells (HSC) reside provides a radioprotective microenvironment that is 2-to 3-fold less radiosensitive than vascular niches. This supports partitioning the whole marrow target between the low haematological cancer risk of irradiating HSC in the endosteum and the vascular niches within central marrow. There is a greater risk of induced bone cancer when irradiating a 50 μm thick peripheral marrow adjacent to the remodelling/reforming portion of the trabecular bone surface, rather than marrow next to the quiescent bone surface. This choice of partitioned bone cancer target is substantiated by the greater radiosensitivity of: (i) Bone with high remodelling rates, (ii) the young, (iii) individuals with hypermetabolic benign diseases of bone, and (iv) the epidemiology of alpha-emitting exposures. Evidence is given to show that the absence of excess bone-cancer in atomic-bomb survivors may be partially related to the extremely low prevalence among Japanese of Paget's disease of bone. Radiation-induced fibrosis and the wound healing response may be implicated in not only radiogenic bone cancers but also leukaemia. A novel biological mechanism for adaptive response, and possibility of dynamic targets, is advocated whereby stem cells migrate from vascular niches to stress-mitigated, hypoxic niches. PMID:21204614

Loss of trabeculae by mechano-biological means may explain rapid bone loss in osteoporosis.

PubMed

Mulvihill, Brianne M; McNamara, Laoise M; Prendergast, Patrick J

2008-10-06

Osteoporosis is characterized by rapid and irreversible loss of trabecular bone tissue leading to increased bone fragility. In this study, we hypothesize two causes for rapid loss of bone trabeculae; firstly, the perforation of trabeculae is caused by osteoclasts resorbing a cavity so deep that it cannot be refilled and, secondly, the increases in bone tissue elastic modulus lead to increased propensity for trabecular perforation. These hypotheses were tested using an algorithm that was based on two premises: (i) bone remodelling is a turnover process that repairs damaged bone tissue by resorbing and returning it to a homeostatic strain level and (ii) osteoblast attachment is under biochemical control. It was found that a mechano-biological algorithm based on these premises can simulate the remodelling cycle in a trabecular strut where damaged bone is resorbed to form a pit that is subsequently refilled with new bone. Furthermore, the simulation predicts that there is a depth of resorption cavity deeper than which refilling of the resorption pits is impossible and perforation inevitably occurs. However, perforation does not occur by a single fracture event but by continual removal of microdamage after it forms beneath the resorption pit. The simulation also predicts that perforations would occur more easily in trabeculae that are more highly mineralized (stiffer). Since both increased osteoclast activation rates and increased mineralization have been measured in osteoporotic bone, either or both may contribute to the rapid loss of trabecular bone mass observed in osteoporotic patients.

Evaluation of bone repair in the femur of rats submitted to laser therapy in different wavelengths: An image segmentation method of analysis

NASA Astrophysics Data System (ADS)

Queiroga, A. S.; Sousa, F. B.; Araújo, J. M. S.; Santos, S. D.; Sousa, C. D'f. S.; Quintans, T. C.; Almeida, T. P.; Nonaka, C. F. W.; Batista, L. V.; Limeira Junior, F. A.

2008-09-01

The aim of this study was to histologically assess the effect of laser therapy (LILT, 660 and 780 nm) on the repair of standardized bone defects on the femur of Wistar albinus rats. The sample was composed of 12 Wistar albinus young adult rats of both genders. Three randomized groups were studied: group I (control, n = 4), group II (LILT, 660 nm, n = 4), and group III (LILT, 780 nm, n = 4). Samples were prepared using a bone defect on the left-side femur surface of the animals, with a total dimension of approximately 3 mm3. Groups II and III were irradiated every 48 h from the second application, where the first dose was given immediately after surgery and the second application came 24 h after surgery. The irradiations were applied transcutaneously at four points around the wound for 14 days. At each point, a dose of 50 J/cm2 (2 J) was given ( s ˜ 0.04 cm2, 40 mW) and the total dose per session was 200 J/cm2 (8 J). The sacrifices were made 15 days after surgery and the specimens were routinely processed to wax, serially cut, stained with an H&E stain, and analyzed under light microscopy. The images were submitted to morphometric analysis using the image segmentation method using the K-means algorithm. The data obtained through the morphometric analysis were submitted to statistical analysis using the Tukey test. The results showed that the group treated with laser therapy in the infrared spectrum resulted in an increase in the repair of bone defects when compared with the group treated with the laser in the red spectrum and control group, which, in turn, had a very similar pattern of repair. A statistical significance ( p < 0.01) was observed when comparing the results of group III and the results of Groups I and II. We concluded that the LILT in the infrared spectrum produced a positive biomodulation effect on the repair of bone defects in the femur of rats.

Scala tympani cochleostomy II: topography and histology.

PubMed

Adunka, Oliver F; Radeloff, Andreas; Gstoettner, Wolfgang K; Pillsbury, Harold C; Buchman, Craig A

2007-12-01

To assess intracochlear trauma using two different round window-related cochleostomy techniques in human temporal bones. Twenty-eight human temporal bones were included in this study. In 21 specimens, cochleostomies were initiated inferior to the round window (RW) annulus. In seven bones, cochleostomies were drilled anterior-inferior to the RW annulus. Limited cochlear implant electrode insertions were performed in 19 bones. In each specimen, promontory anatomy and cochleostomy drilling were photographically documented. Basal cochlear damage was assessed histologically and electrode insertion properties were documented in implanted bones. All implanted specimens showed clear scala tympani electrode placements regardless of cochleostomy technique. All 21 inferior cochleostomies were atraumatic. Anterior-inferior cochleostomies resulted in various degrees of intracochlear trauma in all seven bones. For atraumatic opening of the scala tympani using a cochleostomy approach, initiation of drilling should proceed from inferior to the round window annulus, with gradual progression toward the undersurface of the lumen. While cochleostomies initiated anterior-inferior to the round window annulus resulted in scala tympani opening, many of these bones displayed varying degrees of intracochlear trauma that may result in hearing loss. When intracochlear drilling is avoided, the anterior bony margin of the cochleostomy remains a significant intracochlear impediment to in-line electrode insertion.

Influence of Environmental Factors and Relationships between Vanadium, Chromium, and Calcium in Human Bone

PubMed Central

Lanocha-Arendarczyk, Natalia; Kosik-Bogacka, Danuta I.; Kalisinska, Elzbieta; Sokolowski, Sebastian; Kolodziej, Lukasz; Budis, Halina; Safranow, Krzysztof; Kot, Karolina; Ciosek, Zaneta; Tomska, Natalia; Galant, Katarzyna

2016-01-01

The aim of this study was to investigate the impact of environmental factors on the concentrations of vanadium (V), chromium (Cr), and calcium (Ca) and to examine the synergistic or antagonistic relationships between these metals, in cartilage (C), cortical bone (CB), and spongy bone (SB) samples obtained following hip joint surgery on patients with osteoarthritis in NW Poland. We found significantly higher concentrations of V and Cr in spongy bone in patients who consumed game meat and also those with prosthetic implants. Chromium levels were significantly lower in patients with kidney diseases. The greatest positive correlations were found between spongy bone V and (i) the amount of consumed beer and (ii) seafood diet. Correlation analysis also showed a significant correlation between Cr levels and seafood diet. To a certain extent these results indicate that the concentrations of V, Cr, and Ca in the human hip joint tissues are connected with occupational exposure, kidney diseases, diet containing game meat, sea food, beer, and the presence of implants. Furthermore, we noted new types of interactions in specific parts of the femoral head. Vanadium may contribute to the lower bone Ca levels, especially in the external parts (cartilage and cortical bone). PMID:27294138

Influence of Environmental Factors and Relationships between Vanadium, Chromium, and Calcium in Human Bone.

PubMed

Lanocha-Arendarczyk, Natalia; Kosik-Bogacka, Danuta I; Kalisinska, Elzbieta; Sokolowski, Sebastian; Kolodziej, Lukasz; Budis, Halina; Safranow, Krzysztof; Kot, Karolina; Ciosek, Zaneta; Tomska, Natalia; Galant, Katarzyna

2016-01-01

The aim of this study was to investigate the impact of environmental factors on the concentrations of vanadium (V), chromium (Cr), and calcium (Ca) and to examine the synergistic or antagonistic relationships between these metals, in cartilage (C), cortical bone (CB), and spongy bone (SB) samples obtained following hip joint surgery on patients with osteoarthritis in NW Poland. We found significantly higher concentrations of V and Cr in spongy bone in patients who consumed game meat and also those with prosthetic implants. Chromium levels were significantly lower in patients with kidney diseases. The greatest positive correlations were found between spongy bone V and (i) the amount of consumed beer and (ii) seafood diet. Correlation analysis also showed a significant correlation between Cr levels and seafood diet. To a certain extent these results indicate that the concentrations of V, Cr, and Ca in the human hip joint tissues are connected with occupational exposure, kidney diseases, diet containing game meat, sea food, beer, and the presence of implants. Furthermore, we noted new types of interactions in specific parts of the femoral head. Vanadium may contribute to the lower bone Ca levels, especially in the external parts (cartilage and cortical bone).

Engineered decellularized matrices to instruct bone regeneration processes.

PubMed

Papadimitropoulos, Adam; Scotti, Celeste; Bourgine, Paul; Scherberich, Arnaud; Martin, Ivan

2015-01-01

Despite the significant progress in the field of bone tissue engineering, cell-based products have not yet reached the stage of clinical adoption. This is due to the uncertain advantages from the standard-of-care, combined with challenging cost-and regulatory-related issues. Novel therapeutic approaches could be based on exploitation of the intrinsic regenerative capacity of bone tissue, provided the development of a deeper understanding of its healing mechanisms. While it is well-established that endogenous progenitors can be activated toward bone formation by overdoses of single morphogens, the challenge to stimulate the healing processes by coordinated and controlled stimulation of specific cell populations remains open. Here, we review the recent approaches to generate osteoinductive materials based on the use of decellularized extracellular matrices (ECM) as reservoirs of multiple factors presented at physiological doses and through the appropriate ligands. We then propose the generation of customized engineered and decellularized ECM (i) as a tool to better understand the processes of bone regeneration and (ii) as safe and effective "off-the-shelf" bone grafts for clinical use. This article is part of a Special Issue entitled Stem Cells and Bone. Copyright © 2014 Elsevier Inc. All rights reserved.

A novel strontium(II)-modified calcium phosphate bone cement stimulates human-bone-marrow-derived mesenchymal stem cell proliferation and osteogenic differentiation in vitro.

PubMed

Schumacher, M; Lode, A; Helth, A; Gelinsky, M

2013-12-01

In the present study, the in vitro effects of novel strontium-modified calcium phosphate bone cements (SrCPCs), prepared using two different approaches on human-bone-marrow-derived mesenchymal stem cells (hMSCs), were evaluated. Strontium ions, known to stimulate bone formation and therefore already used in systemic osteoporosis therapy, were incorporated into a hydroxyapatite-forming calcium phosphate bone cement via two simple approaches: incorporation of strontium carbonate crystals and substitution of Ca(2+) by Sr(2+) ions during cement setting. All modified cements released 0.03-0.07 mM Sr(2+) under in vitro conditions, concentrations that were shown not to impair the proliferation or osteogenic differentiation of hMSCs. Furthermore, strontium modification led to a reduced medium acidification and Ca(2+) depletion in comparison to the standard calcium phosphate cement. In indirect and direct cell culture experiments with the novel SrCPCs significantly enhanced cell proliferation and differentiation were observed. In conclusion, the SrCPCs described here could be beneficial for the local treatment of defects, especially in the osteoporotic bone. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Cell therapy of pseudarthrosis.

PubMed

Bastos Filho, Ricardo; Lermontov, Simone; Borojevic, Radovan; Schott, Paulo Cezar; Gameiro, Vinicius Schott; Granjeiro, José Mauro

2012-01-01

To assess the safety and efficiency of cell therapy for pseudarthrosis. Implant of the bone marrow aspirate was compared to mononuclear cells purified extemporaneously using the Sepax(®) equipment. Six patients with nonunion of the tibia or femur were treated. Four received a percutaneous infusion of autologous bone marrow aspirated from the iliac crest, and two received autologous bone marrow mononuclear cells separated from the aspirate with the Sepax(®). The primary fixation method was unchanged, and the nonunion focus was not exposed. Physical examination and radiographies were performed 2, 4 and 6 months after the treatment by the same physician. After consolidation of the fracture the satisfaction of the patients was estimated using the adapted QALY scale. No complications occurred as a result of the referred procedures. Bone consolidation was obtained in all cases within 3 to 24 weeks. The degree of patient satisfaction before and after bone consolidation was assessed, with the average value increasing from two to nine (p=0.0156). We conclude that the proposed method is effective and safe for the treatment of nonunion of long bones regardless of the stabilization method used. Level of Evidence II, Prospective Comparative Study.

Wideband Single Crystal Transducer for Bone Characterization

NASA Technical Reports Server (NTRS)

Sahul, Raffi

2015-01-01

Phase II objectives: Optimize the Phase I transducer for sensitivity; Test different transmit signals for optimum performance; Demonstrate compatibility with electronics; Confirm additional transducer capabilities over conventional systems by calibrating with other methods.

Autologous Stem Cell Transplant Followed By Maintenance Therapy in Treating Elderly Patients With Multiple Myeloma

ClinicalTrials.gov

2018-02-27

Extramedullary Plasmacytoma; Isolated Plasmacytoma of Bone; Light Chain Deposition Disease; Primary Systemic Amyloidosis; Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage III Multiple Myeloma

An investigation of the inelastic behaviour of trabecular bone during the press-fit implantation of a tibial component in total knee arthroplasty.

PubMed

Kelly, N; Cawley, D T; Shannon, F J; McGarry, J P

2013-11-01

The stress distribution and plastic deformation of peri-prosthetic trabecular bone during press-fit tibial component implantation in total knee arthroplasty is investigated using experimental and finite element techniques. It is revealed that the computed stress distribution, implantation force and plastic deformation in the trabecular bone is highly dependent on the plasticity formulation implemented. By incorporating pressure dependent yielding using a crushable foam plasticity formulation to simulate the trabecular bone during implantation, highly localised stress concentrations and plastic deformation are computed at the bone-implant interface. If the pressure dependent yield is neglected using a traditional von Mises plasticity formulation, a significantly different stress distribution and implantation force is computed in the peri-prosthetic trabecular bone. The results of the study highlight the importance of: (i) simulating the insertion process of press-fit stem implantation; (ii) implementing a pressure dependent plasticity formulation, such as the crushable foam plasticity formulation, for the trabecular bone; (iii) incorporating friction at the implant-bone interface during stem insertion. Simulation of the press-fit implantation process with an appropriate pressure dependent plasticity formulation should be implemented in the design and assessment of arthroplasty prostheses. Copyright © 2013 IPEM. Published by Elsevier Ltd. All rights reserved.

ESWT and alendronate sodium demonstrate equal protective effects in osteoarthritis of the knee

NASA Astrophysics Data System (ADS)

Wang, Ching-Jen; Chou, Wen-Yi; Hsu, Shan-Ling; Huang, Chien-Yiu; Cheng, Jai-Hong

2016-01-01

This study compared the effects of extracorporeal shock wave therapy (ESWT) and alendronate sodium (alendronate) in osteoarthritis (OA) of rat knees. The control group was subjected to a sham surgery and did not receive either ESWT or alendronate treatment. The OA group underwent anterior cruciate ligament transection (ACLT) and medial meniscectomy (MM) surgery and did not receive either ESWT or alendronate. The ESWT group underwent ACLT and MM surgery and received ESWT after the surgery. The alendronate group received alendronate after ACLT and MM surgery. The evaluations included radiograph, bone mineral density (BMD), serum C-telopeptide collagen II (CTX-II), cartilage oligomeric protein (COMP), alkaline phosphatase and osteocalcin, histopathological examination and immunohistochemical analysis. Radiographs at 12 weeks showed pronounced OA changes in the OA group. The BMD values, CTX-II, COMP, alkaline phosphatase and osteocalcin showed no significant difference between ESWT and alendronate groups. In histopathology, the Mankin and Safranin O scores significantly increased in the OA, ESWT and alendronate groups, but without any significant difference between the ESWT and alendronate groups. In immunohistochemical analysis, the von Willebrand factor (vWF), vascular endothelial factor (VEGF), soluble vascular cell adhesion molecule (sVCAM), proliferating cell nuclear antigen (PCNA), bone morphogenetic protein 2 (BMP-2), and osteocalcin expressions in articular cartilage and subchondral bone showed a significant decrease in the OA group, but no difference was noted between the ESWT and alendronate groups. In conclusion, ESWT and alendronate sodium demonstrate equal protective effects from developing osteoarthritis of the knee in rats.

Porous NiTi for bone implants: a review.

PubMed

Bansiddhi, A; Sargeant, T D; Stupp, S I; Dunand, D C

2008-07-01

NiTi foams are unique among biocompatible porous metals because of their high recovery strain (due to the shape-memory or superelastic effects) and their low stiffness facilitating integration with bone structures. To optimize NiTi foams for bone implant applications, two key areas are under active study: synthesis of foams with optimal architectures, microstructure and mechanical properties; and tailoring of biological interactions through modifications of pore surfaces. This article reviews recent research on NiTi foams for bone replacement, focusing on three specific topics: (i) surface modifications designed to create bio-inert porous NiTi surfaces with low Ni release and corrosion, as well as bioactive surfaces to enhance and accelerate biological activity; (ii) in vitro and in vivo biocompatibility studies to confirm the long-term safety of porous NiTi implants; and (iii) biological evaluations for specific applications, such as in intervertebral fusion devices and bone tissue scaffolds. Possible future directions for bio-performance and processing studies are discussed that could lead to optimized porous NiTi implants.

Porous NiTi for bone implants: A review

PubMed Central

Bansiddhi, A.; Sargeant, T.D.; Stupp, S.I.; Dunand, D.C.

2011-01-01

NiTi foams are unique among biocompatible porous metals because of their high recovery strain (due to the shape-memory or superelastic effects) and their low stiffness facilitating integration with bone structures. To optimize NiTi foams for bone implant applications, two key areas are under active study: synthesis of foams with optimal architectures, microstructure and mechanical properties; and tailoring of biological interactions through modifications of pore surfaces. This article reviews recent research on NiTi foams for bone replacement, focusing on three specific topics: (i) surface modifications designed to create bio-inert porous NiTi surfaces with low Ni release and corrosion, as well as bioactive surfaces to enhance and accelerate biological activity; (ii) In vitro and in vivo biocompatibility studies to confirm the long-term safety of porous NiTi implants; and (iii) biological evaluations for specific applications, such as in intervertebral fusion devices and bone tissue scaffolds. Possible future directions for bio-performance and processing studies are discussed that could lead to optimized porous NiTi implants. PMID:18348912

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

PubMed

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

2016-04-01

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

Increasing dietary nitrate has no effect on cancellous bone loss or fecal microbiome in ovariectomized rats.

PubMed

Conley, Melissa N; Roberts, Cooper; Sharpton, Thomas J; Iwaniec, Urszula T; Hord, Norman G

2017-05-01

Studies suggest diets rich in fruit and vegetables reduce bone loss, although the specific compounds responsible are unknown. Substrates for endogenous nitric oxide (NO) production, including organic nitrates and dietary nitrate, may support NO production in age-related conditions, including osteoporosis. We investigated the capability of dietary nitrate to improve NO bioavailability, reduce bone turnover and loss. Six-month-old Sprague Dawley rats [30 ovariectomized (OVX) and 10 sham-operated (sham)] were randomized into three groups: (i) vehicle (water) control, (ii) low-dose nitrate (LDN, 0.1 mmol nitrate/kg bw/day), or (iii) high-dose nitrate (HDN, 1.0 mmol nitrate/kg bw/day) for three weeks. The sham received vehicle. Serum bone turnover markers; bone mass, mineral density, and quality; histomorphometric parameters; and fecal microbiome were examined. Three weeks of LDN or HDN improved NO bioavailability in a dose-dependent manner. OVX resulted in cancellous bone loss, increased bone turnover, and fecal microbiome changes. OVX increased relative abundances of Firmicutes and decreased Bacteroideceae and Alcaligenaceae. Nitrate did not affect the skeleton or fecal microbiome. These data indicate that OVX affects the fecal microbiome and that the gut microbiome is associated with bone mass. Three weeks of nitrate supplementation does not slow bone loss or alter the fecal microbiome in OVX. © 2017 The Authors. Molecular Nutrition & Food Research published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Increasing dietary nitrate has no effect on cancellous bone loss or fecal microbiome in ovariectomized rats

PubMed Central

Conley, Melissa N.; Roberts, Cooper; Sharpton, Thomas J.; Iwaniec, Urszula T.

2017-01-01

Scope Studies suggest diets rich in fruit and vegetables reduce bone loss, although the specific compounds responsible are unknown. Substrates for endogenous nitric oxide (NO) production, including organic nitrates and dietary nitrate, may support NO production in age‐related conditions, including osteoporosis. We investigated the capability of dietary nitrate to improve NO bioavailability, reduce bone turnover and loss. Methods and results Six‐month‐old Sprague Dawley rats [30 ovariectomized (OVX) and 10 sham‐operated (sham)] were randomized into three groups: (i) vehicle (water) control, (ii) low‐dose nitrate (LDN, 0.1 mmol nitrate/kg bw/day), or (iii) high‐dose nitrate (HDN, 1.0 mmol nitrate/kg bw/day) for three weeks. The sham received vehicle. Serum bone turnover markers; bone mass, mineral density, and quality; histomorphometric parameters; and fecal microbiome were examined. Three weeks of LDN or HDN improved NO bioavailability in a dose‐dependent manner. OVX resulted in cancellous bone loss, increased bone turnover, and fecal microbiome changes. OVX increased relative abundances of Firmicutes and decreased Bacteroideceae and Alcaligenaceae. Nitrate did not affect the skeleton or fecal microbiome. Conclusion These data indicate that OVX affects the fecal microbiome and that the gut microbiome is associated with bone mass. Three weeks of nitrate supplementation does not slow bone loss or alter the fecal microbiome in OVX. PMID:28087899

Hydroxyapatite crystals as a bone graft substitute in benign lytic lesions of bone

PubMed Central

Gupta, Anil Kumar; Kumar, Praganesh; Keshav, Kumar; Singh, Anant

2015-01-01

Background: Bone grafts are required to fill a cavity created after curettage of benign lytic lesions of the bone. To avoid the problems associated at donor site with autologous bone graft, we require allograft or bone graft substitutes. We evaluated the healing of lytic lesions after hydroxyapatite (HA) grafting by serial radiographs. Materials and Methods: Forty cases of benign lytic lesions of bone were managed by simple curettage and grafting using HA blocks. Commercially available HA of bovine origin (Surgiwear Ltd., Shahjahanpur, India) was used for this purpose. Mean duration of followup was 34.8 months (range 12–84 months). Mean patient age was 19.05 years (range 3–55 years). Radiological staging of graft incorporation was done as per criteria of Irwin et al. 2001. Results: In our series, two cases were in stage I. A total of 11 cases were in stage II and 27 were in stage III. Graft incorporation was radiologically complete by 15 months. Clinical recovery was observed before radiological healing. The average time taken to return to preoperative function was 3 months. Recurrence was observed in giant cell tumor (n = 3) and chondromyxoid fibroma (n = 1). There was no incidence of graft rejection, collapse, growth plate disturbances or antigenic response. Conclusions: We conclude that calcium HA is biologically acceptable bone graft substitute in the management of benign lytic lesions of bone. PMID:26806973

Atg12 Maintains Skeletal Integrity by Modulating Pro-Osteoclastogenic Signals and Chondrocyte Differentiation

NASA Technical Reports Server (NTRS)

Tahimic, Candice; Bahl, Disha; Shirazi-Fard, Yasaman; Marsh, Timothy; Schreurs, Anne-Sofie; Rael, Victoria E.; Glikbarg, Chloe; Debnath, Jayantha; Globus, Ruth K.

2016-01-01

Weightlessness and radiation, two unique elements of space, profoundly decreases bone mass. This bone loss is attributed to increased activity of bone-resorbing osteoclasts and functional changes in bone-forming osteoblasts, cells that give rise to mature osteocytes. Our long-term goal is to identify signaling pathways that may be targeted to mitigate bone loss in scenarios of space exploration, radiotherapy and accidental radiation exposure. We have previously shown that exposure of MLO-Y4 osteocyte-like cells to simulated space radiation (56Fe) increased the expression of the pro-osteoclastogenic gene rankl and decreased protein levels of LC3B-II, a key player in autophagy. In this current study, we aimed to further elucidate the role of autophagy in maintaining structural integrity of the skeleton. We hypothesize that loss of autophagy in bone leads to an imbalance in pro-osteoclastogenic and pro-osteogenic signals, resulting in net bone loss. To test our hypothesis we performed global postnatal deletion of Atg12 using tamoxifeninducible Cre recombinase under the control of the CAG promoter. Six-week-old CAGCreERT2/ FloxAtg12 animals were treated daily with Tamoxifen or Vehicle (Control, oil only) for five days and euthanasia performed two weeks after the onset of treatment. Percent change in body weights (prior to treatment and at euthanasia) was not significantly different between treatment groups within the same gender. Compared to Vehicle (Control) groups, Tamoxifen (Atg12 iKO) groups showed decreased LC3B-I to II conversion and increased p62 protein levels, consistent with loss of autophagy. Quantitative PCR revealed increased expression of proosteoclastogenic cytokines mcp1 and rankl in bone and marrow respectively in male iKOs compared to male controls. Expression levels of these genes were not significantly altered in the Atg12 iKO females compared to females controls. Microcomputed tomography of tibiae revealed decreased cortical bone volume, cortical thickness and periosteal perimeter consistent with bone loss; and a longer primary spongiosa in male Atg12 iKOs display compared to male controls. These decrements were less pronounced in the female Atg12 iKOs. Cancellous bone structure was not significantly different between iKOs and controls in both genders. Histological analysis also revealed that compared to male controls, male iKOs showed a profound increase in chondrocyte column length of the growth plate with hyper-expansion of both proliferating and hypertrophic zones. Taken together, these findings indicate that autophagy plays an important role in the maintenance of bone structural integrity by mediating the production of proosteoclastogenic signals and regulating chondrocyte proliferation and differentiation.

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

PubMed Central

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

2016-01-01

Introduction Mouse models are used frequently to study effects of bone diseases and genetic determinates of bone strength. Murine bones have an intracortical band of woven bone that is not present in human bones. This band is not obvious under brightfield imaging and not typically analyzed. Due to the band’s morphology and location it has been theorized to be remnant bone from early in life. Furthermore, lamellar and woven bone are well known to have differing mechanical strengths. The purpose of this study was to determine (i) if the band is from early life and (ii) if the woven bone or calcified cartilage contained within the band affect whole bone strength. Woven Bone Origin Studies In twelve to fourteen week old mice, doxycycline was used to label bone formed prior to 3 weeks old. Doxycycline labeling and woven bone patterns on contralateral femora matched well and encompassed an almost identical cross-sectional area. Also, we highlight for the first time in mice the presence of calcified cartilage exclusively within the band. However, calcified cartilage could not be identified on high resolution cone-beam microCT scans when examined visually or by thresholding methods. Mechanical Strength Studies Subsequently, three-point bending was used to analyze the effects of woven bone and calcified cartilage on whole bone mechanics in a cohort of male and female six and 13 week old Balb/C mice. Three-point bending outcomes were correlated with structural and compositional measures using multivariate linear regression. Woven bone composed a higher percent of young bones than older bones. However, calcified cartilage in older bones was twice that of younger bones, which was similar when normalized by area. Area and/or tissue mineral density accounted for >75% of variation for most strength outcomes. Percent calcified cartilage added significant predictive power to maximal force and bending stress. Calcified cartilage and woven bone could have more influence in genetic models where calcified cartilage percent is double our highest value. PMID:27829059

Brain-targeted stem cell gene therapy corrects mucopolysaccharidosis type II via multiple mechanisms.

PubMed

Gleitz, Hélène Fe; Liao, Ai Yin; Cook, James R; Rowlston, Samuel F; Forte, Gabriella Ma; D'Souza, Zelpha; O'Leary, Claire; Holley, Rebecca J; Bigger, Brian W

2018-06-08

The pediatric lysosomal storage disorder mucopolysaccharidosis type II is caused by mutations in IDS, resulting in accumulation of heparan and dermatan sulfate, causing severe neurodegeneration, skeletal disease, and cardiorespiratory disease. Most patients manifest with cognitive symptoms, which cannot be treated with enzyme replacement therapy, as native IDS does not cross the blood-brain barrier. We tested a brain-targeted hematopoietic stem cell gene therapy approach using lentiviral IDS fused to ApoEII (IDS.ApoEII) compared to a lentivirus expressing normal IDS or a normal bone marrow transplant. In mucopolysaccharidosis II mice, all treatments corrected peripheral disease, but only IDS.ApoEII mediated complete normalization of brain pathology and behavior, providing significantly enhanced correction compared to IDS. A normal bone marrow transplant achieved no brain correction. Whilst corrected macrophages traffic to the brain, secreting IDS/IDS.ApoEII enzyme for cross-correction, IDS.ApoEII was additionally more active in plasma and was taken up and transcytosed across brain endothelia significantly better than IDS via both heparan sulfate/ApoE-dependent receptors and mannose-6-phosphate receptors. Brain-targeted hematopoietic stem cell gene therapy provides a promising therapy for MPS II patients. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

Analysis of Biomechanical Effects of Different Sites and Modes of Orthodontic Loading On Arch Expansion in a Preadolescent Mandible: An FEA Study.

PubMed

Haresh, Ajmera Deepal; Pradeep, Singh; Song, Jinlin; Wang, Chao; Fan, Yubo

2018-05-11

The aim of commencing treatment in younger age is to rectify the developing dento-alveolar, skeletal and muscular imbalances. With growing dependence on arch development and expansion, the pendulum is oscillating more towards the non-extraction treatment lately, in resolving constriction and crowding issues. Since, a limited number of attempts have been made for mandibular expansion, this study aimes to evaluate the effect of different modes and sites of loading on the expansion of preadolescent mandible using biomechanics. To address the research purpose, a total of 9 Finite Element models were simulated. Biomechanical response of the mandibular bone and dentition was analyzed under different loading conditions including site and mode, using the simulated FE models. The values of displacement envisaged by the FE models, predict hybrid mode to offer substantial expansion of the mandibular bone as compared to tooth borne and bone borne. In addition, biomechanical effect of site II on mandibular expansion in terms of displacement on X-axis, was significant. In conclusion, the results of our study suggest hybrid mode at site II to be better option for true bony expansion in preadolescent mandible.

Bone metastasis from ovarian cancer. Clinical analysis of 26 cases.

PubMed

Zhang, Min; Sun, Jimei

2013-12-01

To study the clinical characteristics of bone metastasis from ovarian cancer, and facilitate physicians to develop treatment strategies. This retrospective study was carried out in the Provincial Hospital Affiliated to Shandong University, Shandong, China. Twenty-six cases of bone metastasis from ovarian cancer treated between January 2002 and May 2008 were reviewed, and the clinical data were collected. In the current study, the incidence of bone metastasis is 0.82%. Twelve cases of bone metastasis occurred in the cervical vertebra, 10 in the lumbar vertebra, 8 in the pelvis, 7 in the thoracic vertebra, 5 in the limbs, one in the ribs, and 2 in the sternum. Lung metastasis occurred concomitantly in 9 cases, liver metastasis in 5 cases, brain metastasis in 4 cases, splenic metastasis in 3 cases, adrenal metastasis in 2 cases, and lymphatic metastasis in 12 cases. Twenty-three cases (88.5%) of bone metastasis were detected in stage III-IV, and 3 (11.5%) in stage II (p=0.000). The survival time in cases treated using comprehensive therapy was longer than those using radiotherapy or chemotherapy alone (p=0.047). Bone metastasis from ovarian cancer is rare, however, the increasing pathological stage of ovarian cancer may add to the risk of bone metastasis, especially in the cases with lung or lymphatic metastasis. The pelvis and vertebral bone are the most common location of bone metastasis, and comprehensive treatment may improve the survival time of patients.

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

PubMed Central

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

2007-01-01

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

A Phase Ib/II Dose-finding Study to Assess the Safety and Efficacy of LDE225 + INC424 in Patients With MF

ClinicalTrials.gov

2017-07-24

Primary Myelofibrosis; Thrombocythemia, Essential; Thrombocytosis; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Blood Coagulation Disorders; Blood Platelet Disorders; Hemorrhagic Disorders

Serum ionized calcium, intact PTH and novel markers of bone turnover in bedridden elderly patients.

PubMed

Sorva, A; Välimäki, M; Risteli, J; Risteli, L; Elfving, S; Takkunen, H; Tilvis, R

1994-12-01

Chronic immobilization could markedly affect calcium and bone metabolism in elderly people. To investigate this, and to test the theory of 'type II' osteoporosis in bedridden elderly patients with low vitamin D status, 55 such subjects were examined. Serum concentrations of ionized calcium (Ca++), intact parathyrin (PTH) and two novel markers of bone collagen formation (carboxyterminal propeptide of type I procollagen; PICP) and resorption (carboxyterminal crosslinked telopeptide of type I collagen; ICTP) were measured. The effects on these parameters after 40 weeks of supplementation with vitamin D (1000 IU d-1) and/or calcium (1 g d-1) were subsequently prospectively evaluated. Despite low (mean 11.6 nmoll-1) serum 25-hydroxyvitamin D levels (25-OHD), those of 1,25-dihydroxy-vitamin D (1,25-(OH)2D) were mostly normal. Neither correlated with Ca++ or PTH. PTH correlated negatively not only with Ca++ (r = -0.328, P < 0.05) but also with ICTP (r = -0.306, P < 0.05). Mean PICP was normal but ICTP was elevated and tended to correlate positively with Ca++ (r = 0.268, P = 0.06). Vitamin D supplementation did not change PICP or ICTP considerably, despite slightly increased 1,25-(OH)2D and slightly decreased PTH. Ca++ values were normal and remained stable. In conclusion, Ca++ and PTH are poor indicators of vitamin D status in chronically immobilized elderly subjects. Furthermore, the results suggest that the increased bone resorption is not due to 'type II' secondary hyperparathyroidism; rather the resorption is primarily increased. Correction of vitamin D deficiency does not seem to benefit ageing bones unless adequate mechanical loading is provided.

Vitamin D supplementation has minor effects on parathyroid hormone and bone turnover markers in vitamin D-deficient bedridden older patients.

PubMed

Björkman, Mikko; Sorva, Antti; Risteli, Juha; Tilvis, Reijo

2008-01-01

to evaluate the effects of vitamin D supplementation on parathyroid function and bone turnover in aged, chronically immobile patients. a randomised double-blind controlled trial. two hundred and eighteen long-term inpatients aged over 65 years. the patients were randomised into treatment groups of I-III, each receiving 0 IU, 400 IU and 1200 IU cholecalciferol per day, respectively. In case of inadequate consumption of dairy products, patients received a daily calcium substitution of 500 mg. plasma concentrations of 25-hydroxyvitamin D (25-OHD), intact parathyroid hormone (PTH), amino-terminal propeptide of type I procollagen (PINP), a marker of bone formation, and carboxy-terminal telopeptide of type I collagen (ICTP), a marker of bone resorption, were measured at baseline and after 6 months. the patients (age 84.5 years) were chronically bedridden. The baseline 25-OHD was low (23 nmol/l), correlated inversely with PINP, and tended to associate inversely with PTH. The prevalence of vitamin D deficiency (VDD) (25-OHD < 50 nmol/l) was 98% and PTH was elevated in 23% of the patients. Vitamin D supplementation significantly increased 25-OHD concentrations (124% group II, 204% group III) and decreased PTH (-7% group II, -8% group III). PINP tended to decrease, but ICTP tended to increase, and only their ratio decreased significantly. The tendency of ICTP to increase was inconsistent. Changes in 25-OHD correlated inversely with those in PTH and PINP. vitamin D supplementation has minor effects on PTH and bone turnover in chronically immobilised aged patients with VDD. Further comparative studies and meta-analyses are warranted to elucidate the confounding effects of different mobility levels on the benefits of vitamin D supplementation in patients with differing baseline PTH levels.

Disentangling Early Stone Age palimpsests: determining the functional independence of hominid- and carnivore-derived portions of archaeofaunas.

PubMed

Egeland, Charles P; Pickering, Travis Rayne; Domínguez-Rodrigo, Manuel; Brain, C K

2004-11-01

Determining the extent to which hominid- and carnivore-derived components of fossil bone palimpsests formed independently of each other can provide valuable information to paleoanthropologists interested in reconstructing the foraging adaptations of hominids. Because stone tool cutmarks, hammerstone percussion marks, and carnivore tooth marks are usually only imparted on bone during nutrient extraction from a carcass, these bone surface modifications are particularly amenable to the types of analyses that might meet this goal. This study compares the percentage of limb bone specimens that preserve evidence of both hominid- and carnivore-imparted bone damage from actualistic control samples and several Plio-Pleistocene archaeofaunas, including new data from Swartkrans Member 3 (South Africa). We argue that this procedure, which elucidates the degree of hominid-carnivore independence in assemblage formation, will allow researchers to extract for focused analyses high integrity components (hominid and carnivore) from presumably low integrity sites. Comparisons suggest that the hominid- and carnivore-derived components from sites in Olduvai Gorge Bed II (Tanzania), the ST Site Complex at Peninj (Tanzania), and Swartkrans Member 3 formed largely independent of each other, while data from the FLK 22 Zinjanthropus (FLK Zinj) site (Olduvai Gorge Bed I) indicate significant interdependence in assemblage formation. This contrast suggests that some Early Stone Age assemblages (e.g., the Olduvai Gorge Bed II sites, the Peninj ST Site Complex, and Swartkrans Member 3) are probably more useful than others (e.g., FLK Zinj) for assessing the maximal carcass-acquiring abilities of early hominids; in such assemblages as those in the former set, sole hominid-contribution is more confidently discerned and isolated for analysis than in assemblages such as FLK Zinj.

History of internal fixation with plates (part 2): new developments after World War II; compressing plates and locked plates.

PubMed

Hernigou, Philippe; Pariat, Jacques

2017-07-01

The first techniques of operative fracture with plates were developed in the 19th century. In fact, at the beginning these methods consisted of an open reduction of the fracture usually followed by a very unstable fixation. As a consequence, the fracture had to be opened with a real risk of (sometimes lethal) infection, and due to unstable fixation, protection with a cast was often necessary. During the period between World Wars I and II, plates for fracture fixation developed with great variety. It became increasingly recognised that, because a fracture of a long bone normally heals with minimal resorption at the bone ends, this may result in slight shortening and collapse, so a very rigid plate might prevent such collapse. However, as a consequence, delayed healing was observed unless the patient was lucky enough to have the plate break. One way of dealing with this was to use a slotted plate in which the screws could move axially, but the really important advance was recognition of the role of compression. After the first description of compression by Danis with a "coapteur", Bagby and Müller with the AO improved the technique of compression. The classic dynamic compression plates from the 1970s were the key to a very rigid fixation, leading to primary bone healing. Nevertheless, the use of strong plates resulted in delayed union and the osteoporosis, cancellous bone, comminution, and/or pathological bone resulted in some failures due to insufficient stability. Finally, new devices represented by locking plates increased the stability, contributing to the principles of a more biological osteosynthesis while giving enough stability to allow immediate full weight bearing in some patients.

Novel use of gamma correction for precise (99m)Tc-HDP pinhole bone scan diagnosis and classification of knee occult fractures.

PubMed

Bahk, Yong-Whee; Jeon, Ho-Seung; Kim, Jang Min; Park, Jung Mee; Chung, Yong-An; Kim, E Edmund; Kim, Sung-Hoon; Chung, Soo-Kyo

2010-08-01

The aim of this study was to introduce gamma correction pinhole bone scan (GCPBS) to depict specific signs of knee occult fractures (OF) on (99m)Tc-hydroxydiphosphonate (HDP) scan. Thirty-six cases of six different types of knee OF in 27 consecutive patients (male = 20, female = 7, and age = 18-86 years) were enrolled. The diagnosis was made on the basis of a history of acute or subacute knee trauma, local pain, tenderness, cutaneous injury, negative conventional radiography, and positive magnetic resonance imaging (MRI). Because of the impracticability of histological verification of individual OF, MRI was utilized as a gold standard of diagnosis and classification. All patients had (99m)Tc-HDP bone scanning and supplementary GCPBS. GCPBS signs were correlated and compared with those of MRI. The efficacy of gamma correction of ordinary parallel collimator and pinhole collimator scans were collated. Gamma correction pinhole bone scan depicted the signs characteristic of six different types of OF. They were well defined stuffed globular tracer uptake in geographic I fractures (n = 9), block-like uptake in geographic II fractures (n = 7), simple or branching linear uptake in linear cancellous fractures (n = 4), compression in impacted fractures (n = 2), stippled-serpentine uptake in reticular fractures (n = 11), and irregular subcortical uptake in osteochondral fractures (n = 3). All fractures were equally well or more distinctly depicted on GCPBS than on MRI except geographic II fracture, the details of which were not appreciated on GCPBS. Parallel collimator scan also yielded to gamma correction, but the results were inferior to those of the pinhole scan. Gamma correction pinhole bone scan can depict the specific diagnostic signs in six different types of knee occult fractures. The specific diagnostic capability along with the lower cost and wider global availability of bone scanning would make GCPBS an effective alternative.

Efficacy of different levels of Escherichia coli phytase in broiler diets with a reduced P content.

PubMed

Kozłowski, K; Jankowski, J; Jeroch, H

2010-01-01

Escherichia coli-derived 6-phytase expressed in Pichia pastoris (Optiphos) was added to broiler rations with considerably reduced levels of phosphorus (by 1.5 g/kg). This experiment, performed over a five-week period, involved Ross 308 male chickens kept in battery cages. Each group was divided into 9 subgroups, each of 9 chickens (81 birds per treatment). Birds were allocated to a positive control group (I), a negative control group (II) and three phytase-supplemented groups (III-V--the diet as in group II + 250, 500 and 750 FTU Escherichia coli phytase/kg feed, respectively). The major components of starter and grower diets were corn, soybean and wheat meals. Starter and grower diets (in meal form) contained 6.73 and 6.05 g total P/kg, 4.05 and 3.46 g available P (aP)/kg, respectively, in group I, and 5.23 and 4.55 total P/kg, 2.54 g and 1.95 g aP /kg, respectively, in groups II-V. Phytase efficacy was evaluated based on performance results, carcass quality and bone mineralization. P reduction in group II decreased weight gains by 9.1% and increased feed conversion by approximately 8.4%, compared with group I. Diet supplementation with phytase in groups IV and V significantly compensated for the decrease in performance observed in group II. The differences in dressing percentage between group II and groups III and V were significant. Phosphorus reduction in the diets negatively influenced the process of bone mineralization, which was enhanced by phytase supplementation.

Repair of articular osteochondral defects of the knee joint using a composite lamellar scaffold.

PubMed

Lv, Y M; Yu, Q S

2015-04-01

The major problem with repair of an articular cartilage injury is the extensive difference in the structure and function of regenerated, compared with normal cartilage. Our work investigates the feasibility of repairing articular osteochondral defects in the canine knee joint using a composite lamellar scaffold of nano-ß-tricalcium phosphate (ß-TCP)/collagen (col) I and II with bone marrow stromal stem cells (BMSCs) and assesses its biological compatibility. The bone-cartilage scaffold was prepared as a laminated composite, using hydroxyapatite nanoparticles (nano-HAP)/collagen I/copolymer of polylactic acid-hydroxyacetic acid as the bony scaffold, and sodium hyaluronate/poly(lactic-co-glycolic acid) as the cartilaginous scaffold. Ten-to 12-month-old hybrid canines were randomly divided into an experimental group and a control group. BMSCs were obtained from the iliac crest of each animal, and only those of the third generation were used in experiments. An articular osteochondral defect was created in the right knee of dogs in both groups. Those in the experimental group were treated by implanting the composites consisting of the lamellar scaffold of ß-TCP/col I/col II/BMSCs. Those in the control group were left untreated. After 12 weeks of implantation, defects in the experimental group were filled with white semi-translucent tissue, protruding slightly over the peripheral cartilage surface. After 24 weeks, the defect space in the experimental group was filled with new cartilage tissues, finely integrated into surrounding normal cartilage. The lamellar scaffold of ß-TCP/col I/col II was gradually degraded and absorbed, while new cartilage tissue formed. In the control group, the defects were not repaired. This method can be used as a suitable scaffold material for the tissue-engineered repair of articular cartilage defects. Cite this article: Bone Joint Res 2015;4:56-64. ©2015 The British Editorial Society of Bone & Joint Surgery.

Comparison of applying particulate demineralized bone matrix (DBM), putty DBM and open flap debridement in periodontal horizontal bone defects. A 12-month longitudinal, multi-centre, triple-blind, split-mouth, randomized, controlled clinical study. Part 2 - evaluation of the interdental soft tissue.

PubMed

Kaya, Y; Yalim, M; Bahçecitapar, M; Baloş, K

2009-07-01

To date, there have been many studies clinically evaluating periodontal regenerative procedures by the help of routinely used hard and soft tissue parameters; however, these parameters are not capable of assessing interdental soft tissue located above the regenerative periodontal surgery area. The purpose of this study was to assess interproximal soft tissue changes following application of (i) particulate form demineralized bone matrix (DBM), (ii) putty form DBM and (ii) open flap debridement (OFD, control), using modified curtain technique in the treatment of interproximal suprabony (horizontal) defects located in anterior maxillary region, as previously reported. Twenty-five chronic periodontitis patients with 125 interproximal surgery sites (radiologically >or=4 mm horizontal bone defect) were also participate in this second stage of the triple-blind, split mouth, randomized, controlled clinical trial. Surgery sites were assessed by (i) plaque index (PI), (ii) gingival index (GI), (iii) the presence of interdental soft tissue clefts or craters and (iv) the loss of interdental papilla height by using papilla presence index (PPI), during the healing period. At the baseline and 3, 6, 9 and 12 months after the operations, these measurements were repeated. In all groups, there is a significant increase in the prevalence of soft tissue cleft and crater formation (P < 0.01), with increase in PI and GI scores at interdental soft tissue defect areas (P < 0.001), 3 months after the operations. There was also an increase in PPI scores after the operations in all treatment groups (P < 0.01). Three procedures affected the interproximal soft tissues similarly. There was no significant difference among groups in terms of all parameters (P > 0.05). Particulate DBM, putty DBM and OFD demostrated similar interproximal soft tissue changes especially increasing interproximal PI and GI scores in 3 months follow-up.

Fluoroscopy-guided retrograde core drilling and cancellous bone grafting in osteochondral defects of the talus.

PubMed

Anders, Sven; Lechler, Philipp; Rackl, Walter; Grifka, Joachim; Schaumburger, Jens

2012-08-01

In undetached osteochondral lesions (OCL) of the talus both revitalisation of the subchondral necrosis and cartilage preservation are essential. For these cases, we assess the results of minimally invasive retrograde core drilling and cancellous bone grafting. Forty-one osteochondral lesions of the talus (12x grade I, 22x grade II and 7x grade III according to the Pritsch classification, defect sizes 7-14 mm) in 38 patients (mean age 33.2 years) treated by fluoroscopy-guided retrograde core drilling and autologous cancellous bone grafting were evaluated by clinical scores and MRI. The mean follow-up was 29.0 (±13) months. The AOFAS score increased significantly from 47.3 (±15.3) to 80.8 (±18.6) points. Lesions with intact cartilage (grades I and II) had a tendency to superior results than grade III lesions (83.1 ± 17.3 vs. 69.4 ± 22.2 points, p = 0.07). First-line treatments and open distal tibial growth plates led to significantly better outcomes (each p < 0.05). Age, gender, BMI, time to follow-up, defect localisation or a traumatic origin did not influence the score results. On a visual analogue scale pain intensity reduced from 7.5 (±1.5) to 3.7 (±2.6) while subjective function increased from 4.6 (±2.0) to 8.2 (±2.3) (each p < 0.001). In MRI follow-ups, five of the 41 patients showed a complete bone remodelling. In two cases demarcation was detectable. The technique reported is a highly effective therapeutic option in OCL of the talus with intact cartilage grades I and II. However, second-line treatments and grade III lesions with cracked cartilage surface can not be generally recommended for this procedure.

Peri-implant and systemic effects of high-/low-affinity bisphosphonate-hydroxyapatite composite coatings in a rabbit model with peri-implant high bone turnover

PubMed Central

2012-01-01

Background Hydroxyapatite (HA) coatings composed with bisphosphonates (BPs) which have high mineral-binding affinities have been confirmed to successfully enhance implant stability. However, few previous studies focused on HA coatings composed with low-affinity BPs or on systemic effects of locally released BPs. Methods In this long-term study, we developed two kinds of BP-HA composite coatings using either high-affinity BP (alendronate, ALN) or low-affinity BP (risedronate, RIS). Thirty-six rabbits were divided into three groups according to different coating applications (group I: HA, group II: ALN-HA, and group III: RIS-HA). Implants were inserted into the proximal region of the medullary cavity of the left tibiay. At insertion, 2 × 108 wear particles were injected around implants to induce a peri-implant high bone turnover environment. Both local (left tibias) and systemic (right tibias and lumbar vertebrae) inhibitory effect on bone resorption were compared, including bone-implant integration, bone architecture, bone mineral density (BMD), implant stability, and serum levels of bone turnover markers. Results The results indicated that ALN-HA composite coating, which could induce higher bone-implant contact (BIC) ratio, bone mass augmentation, BMD, and implant stability in the peri-implant region, was more potent on peri-implant bone, while RIS-HA composite coating, which had significant systemic effect, was more potent on non-peri-implant bone, especially lumbar vertebrae. Conclusions It is instructive and meaningful to further clinical studies that we could choose different BP-HA composite coatings according to the patient’s condition. PMID:22686414

A 5-year comparison of marginal bone level following immediate loading of single-tooth implants placed in healed alveolar ridges and extraction sockets in the maxilla.

PubMed

Berberi, Antoine N; Sabbagh, Joseph M; Aboushelib, Moustafa N; Noujeim, Ziad F; Salameh, Ziad A

2014-01-01

The aim of present investigation was to evaluate marginal bone level after 5-year follow-up of implants placed in healed ridges and fresh extraction sockets in maxilla with immediate loading protocol. Thirty-six patients in need of a single-tooth replacement in the anterior maxilla received 42 Astra Tech implants (Astra Tech Implant system™, Dentsply Implants, Mölndal, Sweden). Implants were placed either in healed ridges (group I) or immediately into fresh extraction sockets (group II). Implants were restored and placed into functional loading immediately by using a prefabricated abutment. Marginal bone level relative to the implant reference point was recorded at implant placement, crown cementation, 12, 36, and 60 months following loading using intra-oral radiographs. Measurements were made on the mesial and distal sides of each implant. Overall, two implants were lost from the group II, before final crown cementation: they were excluded from the study. The mean change in marginal bone loss (MBL) after implant placement was 0.26 ± 0.161 mm for 1 year, and 0.26 ± 0.171 mm for 3 years, and 0.21 ± 0.185 mm for 5 years in extraction sockets and was 0.26 ± 0.176 mm for 1 year and 0.21 ± 0.175 mm for 3 years, and 0.19 ± 0.172 mm for 5 years in healed ridges group. Significant reduction of marginal bone was more pronounced in implants inserted in healed ridges (P < 0.041) compared to fresh surgical extraction sockets (P < 0.540). Significant MBL was observed on the mesial side of the implant after cementation of the provisional (P < 0.007) and after 12 months (P < 0.034) compared to the distal side which remained stable for 3 and 5 years observation period. Within the limitations of this study, responses of local bone to immediately loaded implants placed either in extraction sockets or healed ridges were similar. Functional loading technique by using prefabricated abutment placed during the surgery time seems to maintain marginal bone around implant in both healed and fresh extraction sites.

Associations of Escherichia coli K-12 OmpF trimers with rough and smooth lipopolysaccharides

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

Diedrich, D.L.; Stein, M.A.; Schnaitman, C.A.

1990-09-01

The associations of both rough and smooth lipopolysaccharides (LPS) with the OmpF porin of Escherichia coli K-12 were examined in galE strains deleted for ompC. Transformation with pSS37 and growth with galactose conferred the ability to assemble a Shigella dysenteriae O antigen onto the core oligosaccharide of E. coli K-12 LPS. The association of LPS with OmpF trimers was assessed by staining, autoradiography of LPS specifically labeled with (1-14C)galactose, and Western immunoblotting with a monoclonal antibody specific for OmpF trimers. These techniques revealed that the migration distances and multiple banding patterns of OmpF porin trimers in sodium dodecyl sulfate-polyacrylamide gelsmore » were dictated by the chemotype of associated LPS. Expression of smooth LPS caused almost all of the trimeric OmpF to run in gels with a slower mobility than trimers from rough strains. The LPS associated with trimers from a smooth strain differed from the bulk-phase LPS by consisting almost exclusively of molecules with O antigen.« less

Hypofractionated Radiotherapy for Complicated Bone Metastases in Patients with Poor Performance Status: A Phase II International Trial.

PubMed

Silva, Mauricio F; Marta, Gustavo N; Lisboa, Felipe P C; Watte, Guilherme; Trippa, Fabio; Maranzano, Ernesto; da Motta, Neiro W; Popovic, Marko; Ha, Tuan; Burmeister, Bryan; Chow, Edward

2017-06-01

Purpose To evaluate the efficacy and safety of hypofractionated radiotherapy (16 Gy in 2 fractions, 1 week apart) in patients with complicated bone metastases and poor performance status. Methods A prospective single-arm phase II clinical trial was conducted from July 2014 to May 2016. The primary endpoint was pain response as defined in the International Consensus on Palliative Radiotherapy Endpoints. Secondary endpoints included quality of life as measured by quality of life questionnaire (QLQ) PAL-15 and QLQ-BM22 European Organisation for Research and Treatment of Cancer guidelines, pain flare, adverse events, re-irradiation, and skeletal complications. Results Fifty patients were enrolled. There were 23 men with a median age of 58 years (range 26-86). Of the 50 patients, 38 had an extraosseous soft tissue component, 18 needed postsurgical radiation, 3 had neuropathic pain, and 3 had an impending fracture in a weight-bearing bone. At 2 months, 33 patients were alive (66%). Four (12.5%) had a complete response and 12 (37.5%) had a partial response. A statistically significant improvement was seen in the functional interference (p = 0.01) and psychosocial aspects (p = 0.03) of the BM22. No patient had spinal cord compression. One patient required surgery for pathologic fracture, and another re-irradiation. Conclusions Hypofractionated radiotherapy (16 Gy in 2 fractions of 8 Gy 1 week apart) achieved satisfactory pain relief and safety results in patients with complicated bone metastases and poor performance status.

LAG-3 Represents a Marker of CD4+ T Cells with Regulatory Activity in Patients with Bone Fracture.

PubMed

Wang, Jun; Ti, Yunfan; Wang, Yicun; Guo, Guodong; Jiang, Hui; Chang, Menghan; Qian, Hongbo; Zhao, Jianning; Sun, Guojing

2018-04-19

The lymphocyte activation gene 3 (LAG-3) is a CD4 homolog with binding affinity to MHC class II molecules. It is thought that LAG-3 exerts a bimodal function, such that co-ligation of LAG-3 and CD3 could deliver an inhibitory signal in conventional T cells, whereas, on regulatory T cells, LAG-3 expression could promote their inhibitory function. In this study, we investigated the role of LAG-3 expression on CD4 + T cells in patients with long bone fracture. We found that LAG-3 + cells represented approximately 13% of peripheral blood CD4 + T cells on average. Compared to LAG-3 - CD4 + T cells, LAG-3 + CD4 + T cells presented significantly higher Foxp3 and CTLA-4 expression. Directly ex vivo or with TCR stimulation, LAG-3 + CD4 + T cells expressed significantly higher levels of IL-10 and TGF-β than LAG-3 - CD4 + T cells. Interestingly, blocking the LAG-3-MHC class II interaction actually increased the IL-10 expression by LAG-3 + CD4 + T cells. The frequency of LAG-3 + CD4 + T cell was positively correlated with restoration of healthy bone function in long bone fracture patients. These results together suggested that LAG-3 is a marker of CD4 + T cells with regulatory function; at the same time, LAG-3 might have limited the full suppressive potential of Treg cells.

Melorheostosis: case report with 20-year follow-up.

PubMed

Pavone, Vito; Evola, Roberto Francesco; Di Giorgio, Angelo; Ruggieri, Martino; Ardito, Salvatore

2008-05-01

The authors report on a typical case of melorheostosis observed in an 18-year-old man, localized in the II digit of the right hand causing tumefaction and irregular pain. At 20-year follow-up, the patient showed a radiographical slight worsening of the lesion. Radiographic examination showed a mild increase in cortical and endosteal hyperostosis with bone shape alteration in the II digit of the right hand, slight cortical and endosteal hyperostosis at the level of right shoulder girdle involving the humerus. The other part of the skeleton was not affected. Clinical examination revealed swelling and tumefaction of the forefinger of the right hand and reduced articular motion both in proximal and distal interphalangeal joint and metacarpal phalangeal joint. The reminder of the clinical examination was normal. Melorheostosis is an uncommon mesenchymal disorder characterized by a chondral hyperostosis of the long bones associated to a sclerosis of the spongious bone. The etiology of this affection is unknown: the most accredited hypothesis is a developmental anomaly with a sequential sclerotomes distribution. Both genders may be affected, with the long tubular bones of the lower limbs more involved. This anomaly is often asymptomatic but maybe accompanied by pain with a smooth symptom progression and periodic exacerbations. Therapy is mainly symptomatic and comprises anti-inflammatory drugs or surgical approach for removal of soft tissue that may preclude daily activities. This case report demonstrates that melorheostosis is a relatively benign disorder with mildly progressive course.

Sequencing analysis of mutations induced by N-ethyl-N-nitrosourea at different sampling times in mouse bone marrow.

PubMed

Wang, Jianyong; Chen, Tao

2010-03-01

In our previous study (Wang et al., 2004, Toxicol. Sci. 82: 124-128), we observed that the cII gene mutant frequency (MF) in the bone marrow of Big Blue mice showed significant increase as early as day 1, reached the maximum at day 3 and then decreased to a plateau by day 15 after a single dose of carcinogen N-ethyl-N-nitrosourea (ENU) treatment, which is different from the longer mutation manifestation time and the constancy of MFs after reaching their maximum in some other tissues. To determine the mechanism underlying the quick increase in MF and the peak formation in the mutant manifestation, we examined the mutation frequencies and spectra of the ENU-induced mutants collected from different sampling times in this study. The cII mutants from days 1, 3 and 120 after ENU treatment were randomly selected from different animals. The mutation frequencies were 33, 217, 305 and 144 x 10(-6) for control, days 1, 3, and 120, respectively. The mutation spectra at days 1 and 3 were significantly different from that at day 120. Considering that stem cells are responsible for the ultimate MF plateau (day 120) and transit cells are accountable for the earlier MF induction (days 1 or 3) in mouse bone marrow, we conclude that transit cells are much more sensitive to mutation induction than stem cells in mouse bone marrow, which resulted in the specific mutation manifestation induced by ENU.

Multivariate linear regression analysis to identify general factors for quantitative predictions of implant stability quotient values

PubMed Central

Huang, Hairong; Xu, Zanzan; Shao, Xianhong; Wismeijer, Daniel; Sun, Ping; Wang, Jingxiao

2017-01-01

Objectives This study identified potential general influencing factors for a mathematical prediction of implant stability quotient (ISQ) values in clinical practice. Methods We collected the ISQ values of 557 implants from 2 different brands (SICace and Osstem) placed by 2 surgeons in 336 patients. Surgeon 1 placed 329 SICace implants, and surgeon 2 placed 113 SICace implants and 115 Osstem implants. ISQ measurements were taken at T1 (immediately after implant placement) and T2 (before dental restoration). A multivariate linear regression model was used to analyze the influence of the following 11 candidate factors for stability prediction: sex, age, maxillary/mandibular location, bone type, immediate/delayed implantation, bone grafting, insertion torque, I-stage or II-stage healing pattern, implant diameter, implant length and T1-T2 time interval. Results The need for bone grafting as a predictor significantly influenced ISQ values in all three groups at T1 (weight coefficients ranging from -4 to -5). In contrast, implant diameter consistently influenced the ISQ values in all three groups at T2 (weight coefficients ranging from 3.4 to 4.2). Other factors, such as sex, age, I/II-stage implantation and bone type, did not significantly influence ISQ values at T2, and implant length did not significantly influence ISQ values at T1 or T2. Conclusions These findings provide a rational basis for mathematical models to quantitatively predict the ISQ values of implants in clinical practice. PMID:29084260

Effect of the masseter muscle injection of botulinum toxin A on the mandibular bone growth of developmental rats.

PubMed

Seok, Hyun; Kim, Seong-Gon; Kim, Min-Keun; Jang, Insan; Ahn, Janghoon

2018-12-01

The objective of this study was to evaluate the influence of masticatory muscle injection of botulinum toxin type A (BTX-A) on the growth of the mandibular bone in vivo. Eleven Sprague-Dawley rats were used, and BTX-A ( n  = 6) or saline ( n  = 5) was injected at 13 days of age. All injections were given to the right masseter muscle, and the BTX-A dose was 0.5 units. All of the rats were euthanized at 60 days of age. The skulls of the rats were separated and fixed with 10% formalin for micro-computed tomography (micro-CT) analysis. The anthropometric analysis found that the ramus heights and bigonial widths of the BTX-A-injected group were significantly smaller than those of the saline-injected group ( P  < 0.05), and the mandibular plane angle of the BTX-A-injected group was significantly greater than in the saline-injected group ( P  < 0.001). In the BTX-A-injected group, the ramus heights II and III and the mandibular plane angles I and II showed significant differences between the injected and non-injected sides ( P  < 0.05). The BTX-A-injected side of the mandible in the masseter group showed significantly lower mandibular bone growth compared with the non-injected side. BTX-A injection into the masseter muscle influences mandibular bone growth.

A Potential Bone-Targeting Hypotoxic Platinum(II) Complex with an Unusual Cytostatic Mechanism toward Osteosarcoma Cells.

PubMed

Zhang, Zhenqin; Zhu, Zhenzhu; Luo, Cheng; Zhu, Chengcheng; Zhang, Changli; Guo, Zijian; Wang, Xiaoyong

2018-03-19

Osteosarcoma (OS) is the most common primary pediatric bone tumor lethal to children and adolescents. Chemotherapeutic agents such as cisplatin are not effective for OS because of their poor accessibility to this cancer and severe systemic toxicity. In this study, a lipophilic platinum(II) complex bearing a bisphosphonate bone-targeting moiety, cis-[PtL(NH 3 ) 2 Cl]NO 3 {BPP; L = tetraethyl [2-(pyridin-2-yl)ethane-1,1-diyl]bisphosphonate}, was prepared and characterized by NMR, electrospray ionization mass spectrometry, and single-crystal X-ray crystallography. The cytotoxicity of BPP toward OS cell lines U2OS and MG-63 was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. BPP exhibits moderate inhibition against U2OS cells through a mechanism involving both DNA binding and a mevalonate pathway. The acute toxicity of BPP to mice is 7-fold lower than that of cisplatin. The relative low systemic toxicity may result from the steric hindrance of the ligand, which blocks BPP approaching the bases of DNA. The results suggest that incorporating bisphosphonates into a platinum complex not only enhances its bone-targeting property but also minimizes its reactivity toward DNA and thereby lowers the systematic toxicity of the complex. The diminished cytotoxicity of BPP could be compensated for by increasing the therapeutic dose with marginal harm. This strategy provides a new possibility for overcoming the ineffectiveness and systemic toxicity of platinum drugs in the treatment of OS.

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

NASA Astrophysics Data System (ADS)

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

2015-03-01

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

Characterization of renal amyloid derived from the variable region of the lambda light chain subgroup II.

PubMed Central

Picken, M. M.; Gallo, G.; Buxbaum, J.; Frangione, B.

1986-01-01

Amyloid fibrils were extracted from the kidney of a patient (CHE) shown to have tetramers and dimers of a monoclonal lambda light chain in his serum, and whose bone marrow cells in short-term culture synthesized these forms and a smaller lambda fragment of approximately 10,000 to 12,000 daltons. Biochemical and serologic analysis of a fraction of a size (obtained from amyloid fibrils extracted from the kidney) similar to that synthesized by the bone marrow cells revealed a light chain fragment corresponding to the amino terminal end of the variable region of the lambda light chain subgroup II. The presence of similarly sized short fragments of lambda light chain in both the synthesized and deposited protein suggests that aberrant synthesis and/or proteolytic degradation may play a pathogenetic role in the process of amyloidogenesis. Images Figure 1 PMID:3089021

Fkbp10 Deletion in Osteoblasts leads to Qualitative Defects in Bone

PubMed Central

Lietman, Caressa D.; Lim, Joohyun; Grafe, Ingo; Chen, Yuqing; Ding, Hao; Bi, Xiaohong; Ambrose, Catherine G.; Fratzl-Zelman, Nadja; Roschger, Paul; Klaushofer, Klaus; Wagermaier, Wolfgang; Schmidt, Ingo; Fratzl, Peter; Rai, Jyoti; Weis, MaryAnn; Eyre, David; Keene, Douglas R.; Krakow, Deborah; Lee, Brendan H.

2017-01-01

Osteogenesis Imperfecta (OI), also known as brittle bone disease, displays a spectrum of clinical severity from mild (OI type I) to severe early lethality (OI type II), with clinical features including low bone mass, fractures and deformities. Mutations in the FK506 Binding Protein 10 (FKBP10), gene encoding the 65KDa protein FKBP65, cause a recessive form of OI and Bruck syndrome, the latter being characterized by joint contractures in addition to low bone mass. We previously showed that Fkbp10 expression is limited to bone, tendon and ligaments in postnatal tissues. Furthermore, in both patients and Fkbp10 knockout mice, collagen telopeptide hydroxylysine crosslinking is dramatically reduced. To further characterize the bone specific contributions of Fkbp10, we conditionally ablated FKBP65 in Fkbp10fl/fl mice (Mus musculus; C57BL/6) using the osteoblast specific Col1a1 2.3kb Cre recombinase. Using μCT, histomorphometry and quantitative backscattered electron imaging, we found minimal alterations in the quantity of bone and no differences in the degree of bone matrix mineralization in this model. However, mass spectroscopy of bone collagen demonstrated a decrease in mature, hydroxylysine-aldehyde crosslinking. Furthermore, bone of mutant mice exhibits a reduction in mineral-to-matrix ratio and in crystal size as shown by Raman spectroscopy and small angle x-ray scattering, respectively. Importantly, abnormalities in bone quality were associated with impaired bone biomechanical strength in mutant femurs compared with those of wild type littermates. Taken together, these data suggest that the altered collagen crosslinking through Fkbp10 ablation in osteoblasts primarily leads to a qualitative defect in the skeleton. PMID:28206698

Bone formation at recombinant human bone morphogenetic protein-2-coated titanium implants in the posterior mandible (Type II bone) in dogs.

PubMed

Wikesjö, Ulf M E; Xiropaidis, Andreas V; Qahash, Mohammed; Lim, Won Hee; Sorensen, Rachel G; Rohrer, Michael D; Wozney, John M; Hall, Jan

2008-11-01

Conventional oral/maxillofacial implants reach osseointegration over several months during which the titanium fixtures interact with alveolar bone. The objective of this study was to determine if adsorbing recombinant human bone morphogenetic protein-2 (rhBMP-2) onto a titanium porous oxide (TPO) implant surface might enhance or accelerate local bone formation and support osseointegration in a large animal oral/maxillofacial orthotopic model. Endosseous implants with a TPO surface were installed into the edentulated posterior mandible in eight adult Hound Labrador mongrel dogs. The implant surface had been adsorbed with rhBMP-2 at 0.2 or 4.0 mg/ml. TPO implants without rhBMP-2 served as control. Treatments were randomized between jaw quadrants. Mucosal flaps were advanced and sutured leaving the implants submerged. Clinical and radiographic evaluations were made immediately post-surgery, at day 10 (suture removal), and week 4 and 8 post-surgery. The animals received fluorescent bone markers at week 3, 4, and at week 8 post-surgery, when they were euthanized for histologic analysis. TPO implants coated with rhBMP-2 exhibited dose-dependent bone remodelling including immediate resorption and formation of implant adjacent bone, and early establishment of clinically relevant osseointegration. The resulting bone-implant contact, although clinically respectable, appeared significantly lower for rhBMP-2-coated implants compared with the control [rhBMP-2 (0.2 mg/ml) 43.3+/-10.8%versus 71.7+/-7.8%, p<0.02; rhBMP-2 (4.0 mg/ml) 35.4+/-10.6%versus 68.2+/-11.0%, p<0.03]. rhBMP-2 adsorbed onto TPO implant surfaces initiates dose-dependent peri-implant bone re-modelling resulting in the formation of normal, physiologic bone and clinically relevant osseointegration within 8 weeks.

Acetabular Reconstruction With Femoral Head Autograft After Intraarticular Resection of Periacetabular Tumors is Durable at Short-term Followup.

PubMed

Tang, Xiaodong; Guo, Wei; Yang, Rongli; Yan, Taiqiang; Tang, Shun; Li, Dasen

2017-12-01

Pelvic reconstruction after periacetabular tumor resection is technically difficult and characterized by a high complication rate. Although endoprosthetic replacement can result in immediate postoperative functional recovery, biologic reconstructions with autograft may provide an enhanced prognosis in patients with long-term survival; however, little has been published regarding this approach. We therefore wished to evaluate whether whole-bulk femoral head autograft that is not contaminated by tumor can be used to reconstruct segmental bone defects after intraarticular resection of periacetabular tumors. In a pilot study, we evaluated (1) local tumor control, (2) complications, and (3) postoperative function as measured by the Musculoskeletal Tumor Society score. Between 2009 and 2015, we treated 13 patients with periacetabular malignant or aggressive benign tumors with en bloc resection, bulk femoral head autograft, and cemented THA (with or without a titanium acetabular reconstruction cup), and all were included for analysis here. During that time, the general indications for this approach were (1) patients anticipated to have a good oncologic prognosis and adequate surgical margins to allow this approach, (2) patients whose pelvic bone defects did not exceed two types (Types I + II or Types II + III as defined by Enneking and Dunham), and (3) patients whose medical insurance would not cover what otherwise might have been a pelvic tumor prosthesis. During this period, another 91 patients were treated with pelvic prosthetic replacement, which was our preferred approach. Median followup in this study was 36 months (range, 24-99 months among surviving patients; one patient died 8 months after surgery); no patients were lost to followup. Bone defects were Types II + III in five patients, and Types I + II in eight. After intraarticular resection, ipsilateral femoral head autograft combined with THA was used to reconstruct the segmental bone defect of the acetabulum. In patients with Types I + II resections, the connection between the sacrum and the acetabulum was reestablished with a fibular autograft or a titanium cage filled with dried bone-allograft particles which was enhanced by using a pedicle screw and rod system. Functional evaluation was done in 11 patients who remained alive and maintained the femoral head autograft at final followup; one other patient received secondary resection involving removal of the femoral head autograft and internal fixation, and was excluded from functional evaluation. Endpoints were assessed by chart review. Two patients experienced local tumor recurrence. Finally, eight patients did not show signs of the disease, one patient died of disease for local and distant tumor relapse, and four patients survived, but still had the disease. Three of these four patients had distant metastases without local recurrence and one had local control after secondary resection but still experienced system relapse. We observed the following complications: hematoma (one patient; treated surgically with hematoma clearance), delayed wound healing (one patient; treated by débridement), deep vein thrombosis (one patient), and hip dislocation (one patient; treated with open reduction). The median 1993 Musculoskeletal Tumor Society score was 83% (25 of 30 points; range, 19-29 points), and all patients were community ambulators; one used a cane, three used a walker, and nine did not use any assistive devices. In this small series at short-term followup, we found that reconstruction of segmental bone defects after intraarticular resection of periacetabular tumors with femoral head autograft does not appear to impede local tumor control; complications were in the range of what might be expected in a series of large pelvic reconstructions, and postoperative function was generally good. Level IV, therapeutic study.

Sclerostin Levels and Bone Turnover Markers in Adolescents with Anorexia Nervosa and Healthy Adolescent Girls

PubMed Central

Faje, Alexander T.; Fazeli, Pouneh K.; Katzman, Debra K.; Miller, Karen K.; Breggia, Anne; Rosen, Clifford J.; Mendes, Nara; Klibanski, Anne; Misra, Madhusmita

2012-01-01

Sclerostin, product of the SOST gene, is an important determinant of bone formation and resorption. Adolescents with anorexia nervosa (AN) have low bone density and decreased levels of bone turnover markers. However, sclerostin has not been examined in AN as a potential mediator of impaired bone metabolism. Our study objectives were to (i) assess associations of sclerostin with surrogate bone turnover markers in girls with AN and controls and (ii) examine effects of transdermal estradiol on sclerostin in AN. 69 girls (44 with AN and 25 normal-weight controls) 13–18 years old were studied at baseline. 22 AN girls were randomized to transdermal estradiol (plus cyclic medroxyprogesterone) or placebo in a double-blind study for 12 months. Sclerostin correlated positively with P1NP and CTX in controls (r = 0. 67 and 0. 53, p = 0. 0002 and 0. 005, respectively) but not in AN despite comparable levels at baseline. Changes in sclerostin over twelve months did not differ in girls randomized to estradiol or placebo. The relationship between sclerostin and bone turnover markers is disrupted in adolescent girls with AN. Despite an increase in BMD with estradiol administration in AN, estrogen does not impact sclerostin levels in this group. PMID:22728230

FROM ANEURYSMAL BONE CYST TO TELANGIECTATIC OSTEOSARCOMA WITH METASTASIS IN INGUINAL LYMPH NODES - CASE REPORT.

PubMed

Janevska, Vesna; Spasevska, Liljana; Samardziski, Milan; Nikodinovskai, Violeta; Zhivadinovik, Julija; Trajkovskai, Elizabeta

2015-01-01

Aneurysmal bone cyst is a benign bone lesion composed of blood filled cystic cavities lined by fibrous septa. Its malignant transformation of is a rare event. We report a case of a lesion in the second metatarsal bone in a 29-year-old male, presented as a slight swelling of the right foot. After the curettage had been done, the diagnosis of aneurysmal bone cyst was made but the recurrence occurred 4 years later. The biopsy of the recurrent tumor showed compact neoplastic tissue consistent with diagnosis of giant cell tumor with malignancy. The malignant component was recognized as a high grade sarcoma with osteoid production. A tumor mass with the whole II metatarsal bone was extirpated and a resected part of fibula was transplanted. A year later, another recurrence occurred, an amputation was performed and a teleangiectatic osteosarcoma with ingvinal lymph nodes metastases was diagnosed. No other tumor mass was confirmed, either clinically or by imaging techniques at the time of his third operation. He died 4 months later with multiple pulmonary metastases. We emphasize the importance of team work in order to achieve the accurate diagnosis, highlighting careful radiological examinations, good sampling and awareness of unusual cases in bone tumor pathology.

Local electronic structure and nanolevel hierarchical organization of bone tissue: theory and NEXAFS study

NASA Astrophysics Data System (ADS)

Pavlychev, A. A.; Avrunin, A. S.; Vinogradov, A. S.; Filatova, E. O.; Doctorov, A. A.; Krivosenko, Yu S.; Samoilenko, D. O.; Svirskiy, G. I.; Konashuk, A. S.; Rostov, D. A.

2016-12-01

Theoretical and experimental investigations of native bone are carried out to understand relationships between its hierarchical organization and local electronic and atomic structure of the mineralized phase. The 3D superlattice model of a coplanar assembly of the hydroxyapatite (HAP) nanocrystallites separated by the hydrated nanolayers is introduced to account the interplay of short-, long- and super-range order parameters in bone tissue. The model is applied to (i) predict and rationalize the HAP-to-bone spectral changes in the electronic structure and (ii) describe the mechanisms ensuring the link of the hierarchical organization with the electronic structure of the mineralized phase in bone. To check the predictions the near-edge x-ray absorption fine structure (NEXAFS) at the Ca 2p, P 2p and O 1s thresholds is measured for native bone and compared with NEXAFS for reference compounds. The NEXAFS analysis has demonstrated the essential hierarchy induced HAP-to-bone red shifts of the Ca and P 2p-to-valence transitions. The lowest O 1s excitation line at 532.2 eV in bone is assigned with superposition of core transitions in the hydroxide OH-(H2O) m anions, Ca2+(H2O) n cations, the carboxyl groups inside the collagen and [PO4]2- and [PO4]- anions with unsaturated P-O bonds.

Sphingosine 1-Phosphate- and C-C Chemokine Receptor 2-Dependent Activation of CD4+ Plasmacytoid Dendritic Cells in the Bone Marrow Contributes to Signs of Sepsis-Induced Immunosuppression

PubMed Central

Smirnov, Anna; Pohlmann, Stephanie; Nehring, Melanie; Ali, Shafaqat; Mann-Nüttel, Ritu; Scheu, Stefanie; Antoni, Anne-Charlotte; Hansen, Wiebke; Büettner, Manuela; Gardiasch, Miriam J.; Westendorf, Astrid M.; Wirsdörfer, Florian; Pastille, Eva; Dudda, Marcel; Flohé, Stefanie B.

2017-01-01

Sepsis is the dysregulated response of the host to systemic, mostly bacterial infection, and is associated with an enhanced susceptibility to life-threatening opportunistic infections. During polymicrobial sepsis, dendritic cells (DCs) secrete enhanced levels of interleukin (IL) 10 due to an altered differentiation in the bone marrow and contribute to the development of immunosuppression. We investigated the origin of the altered DC differentiation using murine cecal ligation and puncture (CLP), a model for human polymicrobial sepsis. Bone marrow cells (BMC) were isolated after sham or CLP operation, the cellular composition was analyzed, and bone marrow-derived DCs (BMDCs) were generated in vitro. From 24 h on after CLP, BMC gave rise to BMDC that released enhanced levels of IL-10. In parallel, a population of CD11chiMHCII+CD4+ DCs expanded in the bone marrow in a MyD88-dependent manner. Prior depletion of the CD11chiMHCII+CD4+ DCs from BMC in vitro reversed the increased IL-10 secretion of subsequently differentiating BMDC. The expansion of the CD11chiMHCII+CD4+ DC population in the bone marrow after CLP required the function of sphingosine 1-phosphate receptors and C-C chemokine receptor (CCR) 2, the receptor for C-C chemokine ligand (CCL) 2, but was not associated with monocyte mobilization. CD11chiMHCII+CD4+ DCs were identified as plasmacytoid DCs (pDCs) that had acquired an activated phenotype according to their increased expression of MHC class II and CD86. A redistribution of CD4+ pDCs from MHC class II− to MHC class II+ cells concomitant with enhanced expression of CD11c finally led to the rise in the number of CD11chiMHCII+CD4+ DCs. Enhanced levels of CCL2 were found in the bone marrow of septic mice and the inhibition of CCR2 dampened the expression of CD86 on CD4+ pDCs after CLP in vitro. Depletion of pDCs reversed the bias of splenic DCs toward increased IL-10 synthesis after CLP in vivo. Thus, during polymicrobial sepsis, CD4+ pDCs are activated in the bone marrow and induce functional reprogramming of differentiating BMDC toward an immunosuppressive phenotype. PMID:29218051

Unicameral bone cysts: comparison of percutaneous curettage, steroid, and autologous bone marrow injections.

PubMed

Canavese, Federico; Wright, James G; Cole, William G; Hopyan, Sevan

2011-01-01

The purpose of this study was to compare the outcome of percutaneous curettage with intralesional injection of methylprednisolone and bone marrow for unicameral bone cysts (UBCs). This was a retrospective review of 46 children and adolescents with UBC treated with autologous bone marrow injection, methylprednisolone acetate injection or percutaneous curettage alone. Inclusion criteria were a radiological diagnosis of UBC and at least 24 months follow-up from the last procedure. Healing was determined using Neer/Cole 4-grades rating scale. The 3 treatment groups were comparable with regard to age, sex, location of the cyst, and the number of procedures undertaken. At 2 years follow-up, the proportion of patients with satisfactory healing (Neer/Cole grades I and II) was greatest among those who underwent percutaneous curettage (70%) compared with bone marrow injection (21%) and methylprednisolone acetate injection (41%) (P = 0.03). We found no association between healing and age (P = 0.80) nor between healing and sex (P = 0.61). These results suggest that mechanical disruption of the cyst membrane may be helpful in healing of cysts and that this technique may be preferred to simple intralesional injections. Level III.

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

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

Ishikawa, Jun; Kaisho, Tsuneyasu; Tomizawa, Hitoshi

1995-04-10

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

Cell therapy of pseudarthrosis

PubMed Central

Bastos Filho, Ricardo; Lermontov, Simone; Borojevic, Radovan; Schott, Paulo Cezar; Gameiro, Vinicius Schott; Granjeiro, José Mauro

2012-01-01

Objective To assess the safety and efficiency of cell therapy for pseudarthrosis. Implant of the bone marrow aspirate was compared to mononuclear cells purified extemporaneously using the Sepax® equipment. Methods Six patients with nonunion of the tibia or femur were treated. Four received a percutaneous infusion of autologous bone marrow aspirated from the iliac crest, and two received autologous bone marrow mononuclear cells separated from the aspirate with the Sepax®. The primary fixation method was unchanged, and the nonunion focus was not exposed. Physical examination and radiographies were performed 2, 4 and 6 months after the treatment by the same physician. After consolidation of the fracture the satisfaction of the patients was estimated using the adapted QALY scale. Results No complications occurred as a result of the referred procedures. Bone consolidation was obtained in all cases within 3 to 24 weeks. The degree of patient satisfaction before and after bone consolidation was assessed, with the average value increasing from two to nine (p=0.0156). Conclusion We conclude that the proposed method is effective and safe for the treatment of nonunion of long bones regardless of the stabilization method used. Level of Evidence II, Prospective Comparative Study PMID:24453616

Dual delivery of rhPDGF-BB and bone marrow mesenchymal stromal cells expressing the BMP2 gene enhance bone formation in a critical-sized defect model.

PubMed

Park, Shin-Young; Kim, Kyoung-Hwa; Shin, Seung-Yun; Koo, Ki-Tae; Lee, Yong-Moo; Seol, Yang-Jo

2013-11-01

Bone tissue healing is a dynamic, orchestrated process that relies on multiple growth factors and cell types. Platelet-derived growth factor-BB (PDGF-BB) is released from platelets at wound sites and induces cellular migration and proliferation necessary for bone regeneration in the early healing process. Bone morphogenetic protein-2 (BMP-2), the most potent osteogenic differentiation inducer, directs new bone formation at the sites of bone defects. This study evaluated a combinatorial treatment protocol of PDGF-BB and BMP-2 on bone healing in a critical-sized defect model. To mimic the bone tissue healing process, a dual delivery approach was designed to deliver the rhPDGF-BB protein transiently during the early healing phase, whereas BMP-2 was supplied by rat bone marrow stromal cells (BMSCs) transfected with an adenoviral vector containing the BMP2 gene (AdBMP2) for prolonged release throughout the healing process. In in vitro experiments, the dual delivery of rhPDGF-BB and BMP2 significantly enhanced cell proliferation. However, the osteogenic differentiation of BMSCs was significantly suppressed even though the amount of BMP-2 secreted by the AdBMP2-transfected BMSCs was not significantly affected by the rhPDGF-BB treatment. In addition, dual delivery inhibited the mRNA expression of BMP receptor type II and Noggin in BMSCs. In in vivo experiments, critical-sized calvarial defects in rats showed enhanced bone regeneration by dual delivery of autologous AdBMP2-transfected BMSCs and rhPDGF-BB in both the amount of new bone formed and the bone mineral density. These enhancements in bone regeneration were greater than those observed in the group treated with AdBMP2-transfected BMSCs alone. In conclusion, the dual delivery of rhPDGF-BB and AdBMP2-transfected BMSCs improved the quality of the regenerated bone, possibly due to the modulation of PDGF-BB on BMP-2-induced osteogenesis.

Anabolic action of parathyroid hormone (PTH) does not compromise bone matrix mineral composition or maturation.

PubMed

Vrahnas, Christina; Pearson, Thomas A; Brunt, Athena R; Forwood, Mark R; Bambery, Keith R; Tobin, Mark J; Martin, T John; Sims, Natalie A

2016-12-01

Intermittent administration of parathyroid hormone (PTH) is used to stimulate bone formation in patients with osteoporosis. A reduction in the degree of matrix mineralisation has been reported during treatment, which may reflect either production of undermineralised matrix or a greater proportion of new matrix within the bone samples assessed. To explore these alternatives, high resolution synchrotron-based Fourier Transform Infrared Microspectroscopy (sFTIRM) coupled with calcein labelling was used in a region of non-remodelling cortical bone to determine bone composition during anabolic PTH treatment compared with region-matched samples from controls. 8week old male C57BL/6 mice were treated with vehicle or 50μg/kg PTH, 5 times/week for 4weeks (n=7-9/group). Histomorphometry confirmed greater trabecular and periosteal bone formation and 3-point bending tests confirmed greater femoral strength in PTH-treated mice. Dual calcein labels were used to match bone regions by time-since-mineralisation (bone age) and composition was measured by sFTIRM in six 15μm 2 regions at increasing depth perpendicular to the most immature bone on the medial periosteal edge; this allowed in situ measurement of progressive changes in bone matrix during its maturation. The sFTIRM method was validated in vehicle-treated bones where the expected progressive increases in mineral:matrix ratio and collagen crosslink type ratio were detected with increasing bone maturity. We also observed a gradual increase in carbonate content that strongly correlated with an increase in longitudinal stretch of the collagen triple helix (amide I:amide II ratio). PTH treatment did not alter the progressive changes in any of these parameters from the periosteal edge through to the more mature bone. These data provide new information about how the bone matrix matures in situ and confirm that bone deposited during PTH treatment undergoes normal collagen maturation and normal mineral accrual. Copyright © 2016 Elsevier Inc. All rights reserved.

Nursing Care Hour Standards Study. Part 1. Section B. Patient Classification System Model Development

DTIC Science & Technology

1981-09-01

Measurement/Adult El FI~ [El 1:11] II PIES Form 326e (OT) 1 Novembeti 1978 A-3 sfti= 237 Saline IrrigatioD (Gastric)W uli il 111 Enema: Cleansing Mi...U lIED Dilatation and -Curettage/Assisting Physician ii) El Do~ EI M.1 L or Evacuation Vaginal /Pelvic Examinrations/Assisting Physician ElU L. IE l2...ADMINISTRATION: Oral -QB E ED EE ElE Suppositories Rectal/ Vaginal 1E El El El I ElD Topical MI~II iE Sublingual III ol El El El DIAGNOSTIC TESTS: Bone

Paralysis Episodes in Carbonic Anhydrase II Deficiency.

PubMed

Al-Ibrahim, Alia; Al-Harbi, Mosa; Al-Musallam, Sulaiman

2003-01-01

Carbonic anhydrase II (CAII) deficiency is an autosomal recessive disorder manifest by osteopetrosis, renal tubular acidosis, and cerebral calcification. Other features include growth failure and mental retardation. Complications of the osteopetrosis include frequent bone fractures, cranial nerve compression, and dental mal-occlusion. A hyper-chloremic metabolic acidosis, sometimes with hypokalemia, occurs due to renal tubular acidosis that may be proximal, distal, or more commonly, the combined type. Such patients may present with global hypotonia, muscle weakness or paralysis. We report a case of CA II deficiency with recurrent attacks of acute paralysis which was misdiagnosed initially as Guillian-Barre syndrome.

Management of Type II Odontoid Fracture for Osteoporotic Bone Structure: Preliminary Report.

PubMed

Cosar, Murat; Ozer, A Fahir; Alkan, Bahadır; Guven, Mustafa; Akman, Tarık; Aras, Adem Bozkurt; Ceylan, Davut; Tokmak, Mehmet

2015-01-01

Anterior transodontoid screw fixation technique is generally chosen for the management of type II odontoid fractures. The nonunion of type II odontoid fractures is still a major problem especially in elderly and osteoporotic patients. Eleven osteoporotic type II odontoid fracured patients were presented in this article. We have divided 11 patients in two groups as classical and Ozer's technique. We have also compared (radiologically and clinically) the classical anterior transodontoid screw fixation (group II: 6 cases) and Ozer's transodontoid screw fixation technique (group I: 5 cases) retrospectively. There was no difference regaring the clinical features of the groups. However, the radiological results showed 100% fusion for Ozer's screw fixation technique and 83% fusion for the classical screw fixation technique. In conclusion, we suggest that Ozer's technique may help to increase the fusion capacity for osteoporotic type II odontoid fractures.

Chondroprotective effects of zoledronic acid on articular cartilage in dogs with experimentally induced osteoarthritis.

PubMed

Dearmin, Michael G; Trumble, Troy N; García, Anapatricia; Chambers, Jon N; Budsberg, Steven C

2014-04-01

To assess effects of zoledronic acid on biomarkers, radiographic scores, and gross articular cartilage changes in dogs with induced osteoarthritis. 21 purpose-bred hound-type dogs. The left stifle joint of each dog was examined arthroscopically to determine initial articular cartilage status, which was followed by cranial cruciate ligament (CrCL) transection to induce osteoarthritis. Dogs were assigned to 3 groups (control group, low dose [10 μg of zoledronic acid/kg], or high dose [25 μg of zoledronic acid/kg). Treatments were administered SC every 3 months for 1 year beginning the day after CrCL transection. Serum and synovial fluid samples and radiographs were obtained 0, 1, 3, 6, 9, and 12 months after transection. At 12 months, each joint was scored for cartilage defects. Serum and synovial fluid biomarkers of bone and cartilage turnover (bone-specific alkaline phosphatase, type I and II collagen, carboxy-propeptide of type II collagen, and chondroitin sulfate 846) were analyzed with ELISAs. The high-dose group had fewer total articular defects and lower severity scores in CrCL-transected stifle joints than did the control group. In addition, the high-dose group had significantly less change in collagenase cleavage of type I or II collagen in the synovial fluid at 1 and 3 months after CrCL transection than did the control group and also had greater changes in bone-specific alkaline phosphatase in synovial fluid at 3 months after CrCL transection than did the control group. Zoledronic acid had a chondroprotective effect in dogs with a transected CrCL.

Antitumor effect and toxicity of free rhodium (II) citrate and rhodium (II) citrate-loaded maghemite nanoparticles in mice bearing breast cancer

PubMed Central

2013-01-01

Background Magnetic fluids containing superparamagnetic iron oxide nanoparticles represent an attractive platform as nanocarriers in chemotherapy. Recently, we developed a formulation of maghemite nanoparticles coated with rhodium (II) citrate, which resulted in in vitro cytotoxicity enhanced up to 4.6 times when compared to free rhodium (II) citrate formulation on breast carcinoma cells. In this work, we evaluate the antitumor activity and toxicity induced by these formulations in Balb/c mice bearing orthotopic 4T1 breast carcinoma. Methods Mice were evaluated with regard to the treatments’ toxicity through analyses of hemogram, serum levels of alanine aminotransferase, iron, and creatinine; DNA fragmentation and cell cycle of bone marrow cells; and liver, kidney and lung histology. In addition, the antitumor activity of rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate was verified by tumor volume reduction, histology and immunohistochemistry. Results Regarding the treatments’ toxicity, no experimental groups had alterations in levels of serum ALT or creatinine, and this suggestion was corroborated by the histopathologic examination of liver and kidney of mice. Moreover, DNA fragmentation frequency of bone marrow cells was lower than 15% in all experimental groups. On the other hand, the complexes rhodium (II) citrate-functionalized maghemite and free rhodium (II) citrate led to a marked growth inhibition of tumor and decrease in CD31 and Ki-67 staining. Conclusions In summary, we demonstrated that both rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate formulations exhibited antitumor effects against 4T1 metastatic breast cancer cell line following intratumoral administration. This antitumor effect was followed by inhibition of both cell proliferation and microvascularization and by tumor tissue injury characterized as necrosis and fibrosis. Remarkably, this is the first published report demonstrating the therapeutic efficacy of maghemite nanoparticles coated with rhodium (II) citrate. This treatment prolonged the survival period of treated mice without inducing apparent systemic toxicity, which strengthens its use for future breast cancer therapeutic applications. PMID:23414068

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

Preventive effects of conservative treatment with short-term teriparatide on the progression of vertebral body collapse after osteoporotic vertebral compression fracture.

PubMed

Park, J-H; Kang, K-C; Shin, D-E; Koh, Y-G; Son, J-S; Kim, B-H

2014-02-01

The progression of fractured vertebral collapse is not rare after a conservative treatment of vertebral compression fracture (VCF). Teriparatide has been shown to directly stimulate bone formation and improve bone density, but there is a lack of evidence regarding its use in fracture management. Conservative treatment with short-term teriparatide is effective for decreasing the progression of fractured vertebral body collapse. Few studies have reported on the prevention of collapsed vertebral body progression after osteoporotic VCF. Teriparatide rapidly enhances bone formation and increases bone strength. This study evaluated preventive effects of short-term teriparatide on the progression of vertebral body collapse after osteoporotic VCF. Radiographs of 68 women with single-level osteoporotic VCF at thoracolumbar junction (T11-L2) were reviewed. Among them, 32 patients were treated conservatively with teriparatide (minimum 3 months) (group I), and 36 were treated with antiresorptive (group II). We measured kyphosis and wedge angle of the fractured vertebral body, and ratios of anterior, middle, and posterior heights of the collapsed body to posterior height of a normal upper vertebra were determined. The degree of collapse progression was compared between two groups. The progression of fractured vertebral body collapse was shown in both groups, but the degree of progression was significantly lower in group I than in group II. At the last follow-up, mean increments of kyphosis and wedge angle were significantly lower in group I (4.0° ± 4.2° and 3.6° ± 3.6°) than in group II (6.8° ± 4.1° and 5.8° ± 3.5°) (p = 0.032 and p = 0.037). Decrement percentages of anterior and middle border height were significantly lower in group I (9.6 ± 10.3 and 7.4 ± 7.5 %) than in group II (18.1 ± 9.7 and 13.8 ± 12.2 %) (p = 0.001 and p = 0.025), but not in posterior height (p = 0.086). In female patients with single-level osteoporotic VCF at the thoracolumbar junction, short-term teriparatide treatment did not prevent but did decrease the progression of fractured vertebral body collapse.

Two novel mutations of CLCN7 gene in Chinese families with autosomal dominant osteopetrosis (type II).

PubMed

Zheng, Hui; Shao, Chong; Zheng, Yan; He, Jin-Wei; Fu, Wen-Zhen; Wang, Chun; Zhang, Zhen-Lin

2016-07-01

Autosomal dominant osteopetrosis type II (ADO-II) is a heritable bone disorder characterized by osteosclerosis, predominantly involving the spine (vertebral end-plate thickening, or rugger-jersey spine), the pelvis ("bone-within-bone" structures) and the skull base. Chloride channel 7 (CLCN7) has been reported to be the causative gene. In this study, we aimed to identify the pathogenic mutation in four Chinese families with ADO-II. All 25 exons of the CLCN7 gene, including the exon-intron boundaries, were amplified and sequenced directly in four probands from the Chinese families with ADO-II. The mutation site was then identified in other family members and 250 healthy controls. In family 1, a known missense mutation c.296A>G in exon 4 of CLCN7 was identified in the proband, resulting in a tyrosine (UAU) to cysteine (UGU) substitution at p.99 (Y99C); the mutation was also identified in his affected father. In family 2, a novel missense mutation c.865G>C in exon 10 was identified in the proband, resulting in a valine (GUC) to leucine (CUC) substitution at p.289 (V289L); the mutation was also identified in her healthy mother and sister. In family 3, a novel missense mutation c.1625C>T in exon 17 of CLCN7 was identified in the proband, resulting in an alanine (GCG) to valine (GUG) substitution at p.542 (A542V); the mutation was also identified in her father. In family 4, a hot spot, R767W (c.2299C>T, CGG>TGG), in exon 24 was found in the proband which once again proved the susceptibility of the site or the similar genetic background in different races. Moreover, two novel mutations, V289L and A542V, occurred at a highly conserved position, found by a comparison of the protein sequences from eight vertebrates, and were predicted to have a pathogenic effect by PolyPhen-2 software, which showed "probably damaging" with a score of approximately 1. These mutation sites were not identified in 250 healthy controls. Our present findings suggest that the novel missense mutations V289L and A542V in the CLCN7 gene were responsible for ADO-II in the two Chinese families.

Outcomes of operative treatment of unstable ankle fractures: a comparison of metallic and biodegradable implants.

PubMed

Noh, Jung Ho; Roh, Young Hak; Yang, Bo Gyu; Kim, Seong Wan; Lee, Jun Suk; Oh, Moo Kyung

2012-11-21

Biodegradable implants for internal fixation of ankle fractures may overcome some disadvantages of metallic implants, such as imaging interference and the potential need for additional surgery to remove the implants. The purpose of this study was to evaluate the outcomes after fixation of ankle fractures with biodegradable implants compared with metallic implants. In this prospectively randomized study, 109 subjects with an ankle fracture underwent surgery with metallic (Group I) or biodegradable implants (Group II). Radiographic results were assessed by the criteria of the Klossner classification system and time to bone union. Clinical results were assessed with use of the American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot scale, Short Musculoskeletal Function Assessment (SMFA) dysfunction index, and the SMFA bother index at three, six, and twelve months after surgery. One hundred and two subjects completed the study. At a mean of 19.7 months, there were no differences in reduction quality between the groups. The mean operative time was 30.2 minutes in Group I and 56.4 minutes in Group II (p < 0.001). The mean time to bone union was 15.8 weeks in Group I and 17.6 weeks in Group II (p = 0.002). The mean AOFAS score was 87.5 points in Group I and 84.3 points in Group II at twelve months after surgery (p = 0.004). The mean SMFA dysfunction index was 8.7 points in Group I and 10.5 points in Group II at twelve months after surgery (p = 0.060). The mean SMFA bother index averaged 3.3 points in Group I and 4.6 points in Group II at twelve months after surgery (p = 0.052). No difference existed between the groups with regard to clinical outcomes for the subjects with an isolated lateral malleolar fracture. The outcomes after fixation of bimalleolar ankle fractures with biodegradable implants were inferior to those after fixation with metallic implants in terms of the score on the AOFAS scale and time to bone union. However, the difference in the final AOFAS score between the groups may not be clinically important. The outcomes associated with the use of biodegradable implants for the fixation of isolated lateral malleolar fractures were comparable with those for metallic implants.

Monitoring of bone regeneration process by means of texture analysis

NASA Astrophysics Data System (ADS)

Kokkinou, E.; Boniatis, I.; Costaridou, L.; Saridis, A.; Panagiotopoulos, E.; Panayiotakis, G.

2009-09-01

An image analysis method is proposed for the monitoring of the regeneration of the tibial bone. For this purpose, 130 digitized radiographs of 13 patients, who had undergone tibial lengthening by the Ilizarov method, were studied. For each patient, 10 radiographs, taken at an equal number of postoperative successive time moments, were available. Employing available software, 3 Regions Of Interest (ROIs), corresponding to the: (a) upper, (b) central, and (c) lower aspect of the gap, where bone regeneration was expected to occur, were determined on each radiograph. Employing custom developed algorithms: (i) a number of textural features were generated from each of the ROIs, and (ii) a texture-feature based regression model was designed for the quantitative monitoring of the bone regeneration process. Statistically significant differences (p < 0.05) were derived for the initial and the final textural features values, generated from the first and the last postoperatively obtained radiographs, respectively. A quadratic polynomial regression equation fitted data adequately (r2 = 0.9, p < 0.001). The suggested method may contribute to the monitoring of the tibial bone regeneration process.

Lead and osteoporosis: Mobilization of lead from bone in postmenopausal women

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

Silbergeld, E.K.; Schwartz, J.; Mahaffey, K.

1988-10-01

Although it has been known that humans accumulate lead in bone, mineralized tissue has been considered primarily as a sequestering compartment and not as a site of toxic action for lead. However, experimental data indicate that bone lead can be released during conditions of demineralization, such as pregnancy and lactation. We have examined lead status in women, before and after menopause, using the NHANES II dataset compiled between 1976 and 1980. In 2981 black and white women there was a highly significant increase in both whole blood and calculated plasma lead concentrations after menopause. The results indicate that bone leadmore » is not an inert storage site for absorbed lead. Moreover, lead may interact with other factors in the course of postmenopausal osteoporosis, to aggravate the course of the disease, since lead is known to inhibit activation of vitamin D, uptake of dietary calcium, and several regulatory aspects of bone cell function. The consequences of this mobilization may also be of importance in assessing the risks of maternal lead exposure to fetal and infant health.« less

Gross, radiology and ultrasonographic evaluation of coral post-implantation in sheep femur.

PubMed

Fadilah, A; Zuki, A B Z; Loqman, M Y; Zamri-Saad, M; Norimah, Y; Asnah, H

2004-05-01

The study was carried out to evaluate macroscopically the ability of coral to repair a large size bone defect. A total 12 adult, male sheep were used in the study. The large bone defect (2.5cm x 0.5cm x 0.5cm) was created surgically on the left proximal femur and replaced by a block of coral (Porites sp.). Radiographs were obtained immediately after surgery and at 2, 4, 8 and 12 weeks post-implantation. Ultrasonographic examinations were carried out every 2 weeks after implantation up to 12 weeks using ultrasound machine (TOSHIBA Capasee II) connected with 7MHz frequency transducer. The sheep were euthanased at 2, 4, 8, and 12 weeks post-implantation and the bone examined grossly. Both ultrasonographs and radiographs taken at 8 and 12 weeks showed that the implants had been resorbed and left the space that much reduced in size. There was no sign of implant rejection observed in all animals. The results showed that processed coral has potential to become bone substitute for reconstructive bone surgery.

Deproteinized bovine bone functionalized with the slow delivery of BMP-2 for the repair of critical-sized bone defects in sheep.

PubMed

Liu, Tie; Wu, Gang; Wismeijer, Daniel; Gu, Zhiyuan; Liu, Yuelian

2013-09-01

As an alternative to an autologous bone graft, deproteinized bovine bone (DBB) is widely used in the clinical dentistry. Although DBB provides an osteoconductive scaffold, it is not capable of enhancing bone regeneration because it is not osteoinductive. In order to render DBB osteoinductive, bone morphogenetic protein 2 (BMP-2) has previously been incorporated into a three dimensional reservoir (a biomimetic calcium phosphate coating) on DBB, which effectively promoted the osteogenic response by the slow delivery of BMP-2. The aim of this study was to investigate the therapeutic effectiveness of such coating on the DBB granules in repairing a large cylindrical bone defect (8 mm diameter, 13 mm depth) in sheep. Eight groups were randomly assigned to the bone defects: (i) no graft material; (ii) autologous bone; (iii) DBB only; (iv) DBB mixed with autologous bone; (v) DBB bearing adsorbed BMP-2; (vi) DBB bearing a coating but no BMP-2; (vii) DBB bearing a coating with adsorbed BMP-2; and (viii) DBB bearing a coating-incorporated depot of BMP-2. 4 and 8 weeks after implantation, samples were withdrawn for a histological and a histomorphometric analysis. Histological results confirmed the excellent biocompatibility and osteoconductivity of all the grafts tested. At 4 weeks, DBB mixed with autologous bone or functionalized with coating-incorporated BMP-2 showed more newly-formed bone than the other groups with DBB. At 8 weeks, the volume of newly-formed bone around DBB that bore a coating-incorporated depot of BMP-2 was greatest among the groups with DBB, and was comparable to the autologous bone group. The use of autologous bone and BMP-2 resulted in more bone marrow formation. Multinucleated giant cells were observed in the resorption process around DBB, whereas histomorphometric analysis revealed no significant degradation of DBB. In conclusion, it was shown that incorporating BMP-2 into the calcium phosphate coating of DBB induced strong bone formation around DBB for repairing a critical-sized bone defect. Copyright © 2013 Elsevier Inc. All rights reserved.

Effect of celastrol on bone structure and mechanics in arthritic rats.

PubMed

Cascão, Rita; Vidal, Bruno; Jalmari Finnilä, Mikko Arttu; Lopes, Inês Pascoal; Teixeira, Rui Lourenço; Saarakkala, Simo; Moita, Luis Ferreira; Fonseca, João Eurico

2017-01-01

Rheumatoid arthritis (RA) is characterised by chronic inflammation leading to articular bone and cartilage damage. Despite recent progress in RA management, adverse effects, lack of efficacy and economic barriers to treatment access still limit therapeutic success. Therefore, safer and less expensive treatments that control inflammation and bone resorption are needed. We have previously shown that celastrol is a candidate for RA treatment. We have observed that it inhibits both interleukin (IL)-1β and tumor necrosis factor (TNF) in vitro, and that it has anti-inflammatory properties and ability to decrease synovial CD68+ macrophages in vivo. Herein our goal was to evaluate the effect of celastrol in local and systemic bone loss. Celastrol was administrated intraperitoneally at a dose of 1 µg/g/day to female Wistar adjuvant-induced arthritic rats. Rats were sacrificed after 22 days of disease progression, and blood, femurs, tibiae and paw samples were collected for bone remodelling markers quantification, 3-point bending test, micro-CT analysis, nanoindentation and Fourier transform infrared spectroscopy measurements, and immunohistochemical evaluation. We have observed that celastrol preserved articular structures and decreased the number of osteoclasts and osteoblasts present in arthritic joints. Moreover, celastrol reduced tartrate-resistant acid phosphatase 5b, procollagen type 1 amino-terminal propeptide and C terminal crosslinked telopeptide of type II collagen serum levels. Importantly, celastrol prevented bone loss and bone microarchitecture degradation. Celastrol also preserved bone nanoproperties and mineral content. Additionally, animals treated with celastrol had less fragile bones, as depicted by an increase in maximum load and yield displacement. These results suggest that celastrol reduces both bone resorption and cartilage degradation, and preserves bone structural properties.

Do vegetarians have a normal bone mass?

PubMed

New, Susan A

2004-09-01

Public health strategies targeting the prevention of poor bone health on a population-wide basis are urgently required, with particular emphasis being placed on modifiable factors such as nutrition. The aim of this review was to assess the impact of a vegetarian diet on indices of skeletal integrity to address specifically whether vegetarians have a normal bone mass. Analysis of existing literature, through a combination of observational, clinical and intervention studies were assessed in relation to bone health for the following: lacto-ovo-vegetarian and vegan diets versus omnivorous, predominantly meat diets, consumption of animal versus vegetable protein, and fruit and vegetable consumption. Mechanisms of action for a dietary "component" effect were examined and other potential dietary differences between vegetarians and non-vegetarians were also explored. Key findings included: (i) no differences in bone health indices between lacto-ovo-vegetarians and omnivores; (ii) conflicting data for protein effects on bone with high protein consumption (particularly without supporting calcium/alkali intakes) and low protein intake (particularly with respect to vegan diets) being detrimental to the skeleton; (iii) growing support for a beneficial effect of fruit and vegetable intake on bone, with mechanisms of action currently remaining unclarified. The impact of a "vegetarian" diet on bone health is a hugely complex area since: 1) components of the diet (such as calcium, protein, alkali, vitamin K, phytoestrogens) may be varied; 2) key lifestyle factors which are important to bone (such as physical activity) may be different; 3) the tools available for assessing consumption of food are relatively weak. However, from data available and given the limitations stipulated above, "vegetarians" do certainly appear to have "normal" bone mass. What remains our challenge is to determine what components of a vegetarian diet are of particular benefit to bone, at what levels and under which mechanisms.

Halofuginone attenuates osteoarthritis by inhibition of TGF-β activity and H-type vessel formation in subchondral bone

PubMed Central

Cui, Zhuang; Crane, Janet; Xie, Hui; Jin, Xin; Zhen, Gehua; Li, Changjun; Xie, Liang; Wang, Long; Bian, Qin; Qiu, Tao; Wan, Mei; Xie, Min; Ding, Sheng; Yu, Bin; Cao, Xu

2016-01-01

Objectives Examine whether osteoarthritis (OA) progression can be delayed by halofuginone in anterior cruciate ligament transection (ACLT) rodent models. Methods 3-month-old male C57BL/6J (wild type; WT) mice and Lewis rats were randomised to sham-operated, ACLT-operated, treated with vehicle, or ACLT-operated, treated with halofuginone. Articular cartilage degeneration was graded using the Osteoarthritis Research Society International (OARSI)-modified Mankin criteria. Immunostaining, flow cytometry, RT-PCR and western blot analyses were conducted to detect relative protein and RNA expression. Bone micro CT (μCT) and CT-based microangiography were quantitated to detect alterations of microarchitecture and vasculature in tibial subchondral bone. Results Halofuginone attenuated articular cartilage degeneration and subchondral bone deterioration, resulting in substantially lower OARSI scores. Specifically, we found that proteoglycan loss and calcification of articular cartilage were significantly decreased in halofuginone-treated ACLT rodents compared with vehicle-treated ACLT controls. Halofuginone reduced collagen X (Col X), matrix metalloproteinase-13 and A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS 5) and increased lubricin, collagen II and aggrecan. In parallel, halofuginone-attenuated uncoupled subchondral bone remodelling as defined by reduced subchondral bone tissue volume, lower trabecular pattern factor (Tb.pf) and increased thickness of subchondral bone plate compared with vehicle-treated ACLT controls. We found that halofuginone exerted protective effects in part by suppressing Th17-induced osteoclastic bone resorption, inhibiting Smad2/3-dependent TGF-β signalling to restore coupled bone remodelling and attenuating excessive angiogenesis in subchondral bone. Conclusions Halofuginone attenuates OA progression by inhibition of subchondral bone TGF-β activity and aberrant angiogenesis as a potential preventive therapy for OA. PMID:26470720

Glycation Contributes to Interaction Between Human Bone Alkaline Phosphatase and Collagen Type I.

PubMed

Halling Linder, Cecilia; Enander, Karin; Magnusson, Per

2016-03-01

Bone is a biological composite material comprised primarily of collagen type I and mineral crystals of calcium and phosphate in the form of hydroxyapatite (HA), which together provide its mechanical properties. Bone alkaline phosphatase (ALP), produced by osteoblasts, plays a pivotal role in the mineralization process. Affinity contacts between collagen, mainly type II, and the crown domain of various ALP isozymes were reported in a few in vitro studies in the 1980s and 1990s, but have not attracted much attention since, although such interactions may have important implications for the bone mineralization process. The objective of this study was to investigate the binding properties of human collagen type I to human bone ALP, including the two bone ALP isoforms B1 and B2. ALP from human liver, human placenta and E. coli were also studied. A surface plasmon resonance-based analysis, supported by electrophoresis and blotting, showed that bone ALP binds stronger to collagen type I in comparison with ALPs expressed in non-mineralizing tissues. Further, the B2 isoform binds significantly stronger to collagen type I in comparison with the B1 isoform. Human bone and liver ALP (with identical amino acid composition) displayed pronounced differences in binding, revealing that post-translational glycosylation properties govern these interactions to a large extent. In conclusion, this study presents the first evidence that glycosylation differences in human ALPs are of crucial importance for protein-protein interactions with collagen type I, although the presence of the ALP crown domain may also be necessary. Different binding affinities among the bone ALP isoforms may influence the mineral-collagen interface, mineralization kinetics, and degree of bone matrix mineralization, which are important factors determining the material properties of bone.

The effectiveness of the bone bridge transtibial amputation technique: A systematic review of high-quality evidence.

PubMed

Kahle, Jason T; Highsmith, M Jason; Kenney, John; Ruth, Tim; Lunseth, Paul A; Ertl, Janos

2017-06-01

This literature review was undertaken to determine if commonly held views about the benefits of a bone bridge technique are supported by the literature. Four databases were searched for articles pertaining to surgical strategies specific to a bone bridge technique of the transtibial amputee. A total of 35 articles were identified as potential articles. Authors included methodology that was applied to separate topics. Following identification, articles were excluded if they were determined to be low quality evidence or not pertinent. Nine articles were identified to be pertinent to one of the topics: Perioperative Care, Acute Care, Subjective Analysis and Function. Two articles sorted into multiple topics. Two articles were sorted into the Perioperative Care topic, 4 articles sorted into the Acute Care topic, 2 articles into the Subjective Analysis topic and 5 articles into the Function topic. There are no high quality (level one or two) clinical trials reporting comparisons of the bone bridge technique to traditional methods. There is limited evidence supporting the clinical outcomes of the bone bridge technique. There is no agreement supporting or discouraging the perioperative and acute care aspects of the bone bridge technique. There is no evidence defining an interventional comparison of the bone bridge technique. Current level III evidence supports a bone bridge technique as an equivalent option to the non-bone bridge transtibial amputation technique. Formal level I and II clinical trials will need to be considered in the future to guide clinical practice. Clinical relevance Clinical Practice Guidelines are evidence based. This systematic literature review identifies the highest quality evidence to date which reports a consensus of outcomes agreeing bone bridge is as safe and effective as alternatives. The clinical relevance is understanding bone bridge could additionally provide a mechanistic advantage for the transtibial amputee.

Prevalence of alveolar bone loss in healthy children treated at private pediatric dentistry clinics

PubMed Central

GUIMARÃES, Maria do Carmo Machado; de ARAÚJO, Valéria Martins; AVENA, Márcia Raquel; DUARTE, Daniel Rocha da Silva; FREITAS, Francisco Valter

2010-01-01

Objectives The purpose of this study was to evaluate the prevalence of alveolar bone loss (BL) in healthy children treated at private pediatric dentistry clinics in Brasília, Brazil. Material and Methods The research included 7,436 sites present in 885 radiographs from 450 children. The BL prevalence was estimated by measuring the distance from the cementoenamel junction (CEJ) to alveolar bone crest (ABC). Data were divided in groups: (I) No BL: distance from CEJ to ABC is ≤2 mm; (II) questionable BL (QBL): distance from CEJ to ABC is >2 and <3 mm; (III) definite BL (DBL): distance from CEJ to ABC ≥3 mm. Data were treated by the chi-square nonparametric test and Fisher's exact test (p<0.05). Results Among males, 89.31% were classified in group I, 9.82% were classified in group II and 0.85% in group III. Among females, 93.05%, 6.48% and 0.46% patients were classified in Group I, II and III, respectively. The differences between genders were not statistically significant (Chi-square test, p = 0.375). Group composition according to patients’ age showed that 91.11% of individuals were classified as group I, 8.22% in group II and 0.67% in group III. The differences among the age ranges were not statistically significant (Chi-square test, p = 0.418). The mesial and distal sites showed a higher prevalence of BL in the jaw, QBL (89.80%) and DBL (79.40%), and no significant difference was observed in the distribution of QBL (Fisher’s exact test p = 0.311) and DBL (Fisher’s exact test p = 0.672) in the dental arches. The distal sites exhibited higher prevalence of both QBL (77.56%) and DBL (58.82%). Conclusions The periodontal status of children should never be underestimated because BL occurs even in healthy populations, although in a lower frequency. PMID:20857009

Prevalence of alveolar bone loss in healthy children treated at private pediatric dentistry clinics.

PubMed

Guimarães, Maria do Carmo Machado; de Araújo, Valéria Martins; Avena, Márcia Raquel; Duarte, Daniel Rocha da Silva; Freitas, Francisco Valter

2010-01-01

The purpose of this study was to evaluate the prevalence of alveolar bone loss (BL) in healthy children treated at private pediatric dentistry clinics in Brasília, Brazil. The research included 7,436 sites present in 885 radiographs from 450 children. The BL prevalence was estimated by measuring the distance from the cementoenamel junction (CEJ) to alveolar bone crest (ABC). Data were divided in groups: (I) No BL: distance from CEJ to ABC is <2 mm; (II) questionable BL (QBL): distance from CEJ to ABC is >2 and <3 mm; (III) definite BL (DBL): distance from CEJ to ABC >3 mm. Data were treated by the chi-square nonparametric test and Fisher's exact test (p<0.05). Among males, 89.31% were classified in group I, 9.82% were classified in group II and 0.85% in group III. Among females, 93.05%, 6.48% and 0.46% patients were classified in Group I, II and III, respectively. The differences between genders were not statistically significant (Chi-square test, p = 0.375). Group composition according to patients' age showed that 91.11% of individuals were classified as group I, 8.22% in group II and 0.67% in group III. The differences among the age ranges were not statistically significant (Chi-square test, p = 0.418). The mesial and distal sites showed a higher prevalence of BL in the jaw, QBL (89.80%) and DBL (79.40%), and no significant difference was observed in the distribution of QBL (Fisher's exact test p = 0.311) and DBL (Fisher's exact test p = 0.672) in the dental arches. The distal sites exhibited higher prevalence of both QBL (77.56%) and DBL (58.82%). The periodontal status of children should never be underestimated because BL occurs even in healthy populations, although in a lower frequency.

Three-Dimensional Cone Beam Computed Tomography Volumetric Outcomes of rhBMP-2/Demineralized Bone Matrix versus Iliac Crest Bone Graft for Alveolar Cleft Reconstruction.

PubMed

Liang, Fan; Yen, Stephen L-K; Imahiyerobo, Thomas; Sanborn, Luke; Yen, Leia; Yen, Daniel; Nazarian, Sheila; Jedrzejewski, Breanna; Urata, Mark; Hammoudeh, Jeffrey

2017-10-01

Recent studies indicate that recombinant human bone morphogenetic protein-2 (rhBMP-2) in a demineralized bone matrix scaffold is a comparable alternative to iliac bone autograft in the setting of secondary alveolar cleft repair. Postreconstruction occlusal radiographs demonstrate improved bone stock when rhBMP-2/demineralized bone matrix (DBM) scaffold is used but lack the capacity to evaluate bone growth in three dimensions. This study uses cone beam computed tomography to provide the first clinical evaluation of volumetric and density comparisons between these two treatment modalities. A prospective study was conducted with 31 patients and 36 repairs of the alveolar cleft over a 2-year period. Twenty-one repairs used rhBMP-2/DBM scaffold and 14 repairs used iliac bone grafting. Postoperatively, occlusal radiographs were obtained at 3 months to evaluate bone fill; cone beam computed tomographic images were obtained at 6 to 9 months to compare volumetric and density data. At 3 months, postoperative occlusal radiographs demonstrated that 67 percent of patients receiving rhBMP-2/DBM scaffold had complete bone fill of the alveolus, versus 56 percent of patients in the autologous group. In contrast, cone beam computed tomographic data showed 31.6 percent (95 percent CI, 24.2 to 38.5 percent) fill in the rhBMP-2 group compared with 32.5 percent (95 percent CI, 22.1 to 42.9 percent) in the autologous population. Density analysis demonstrated identical average values between the groups (1.38 g/cc). These data demonstrate comparable bone regrowth and density values following secondary alveolar cleft repair using rhBMP-2/DBM scaffold versus autologous iliac bone graft. Cone beam computed tomography provides a more nuanced understanding of true bone regeneration within the alveolar cleft that may contribute to the information provided by occlusal radiographs alone. Therapeutic, II.

Melanocortin 1 receptor-signaling deficiency results in an articular cartilage phenotype and accelerates pathogenesis of surgically induced murine osteoarthritis.

PubMed

Lorenz, Julia; Seebach, Elisabeth; Hackmayer, Gerit; Greth, Carina; Bauer, Richard J; Kleinschmidt, Kerstin; Bettenworth, Dominik; Böhm, Markus; Grifka, Joachim; Grässel, Susanne

2014-01-01

Proopiomelanocortin-derived peptides exert pleiotropic effects via binding to melanocortin receptors (MCR). MCR-subtypes have been detected in cartilage and bone and mediate an increasing number of effects in diathrodial joints. This study aims to determine the role of MC1-receptors (MC1) in joint physiology and pathogenesis of osteoarthritis (OA) using MC1-signaling deficient mice (Mc1re/e). OA was surgically induced in Mc1re/e and wild-type (WT) mice by transection of the medial meniscotibial ligament. Histomorphometry of Safranin O stained articular cartilage was performed with non-operated controls (11 weeks and 6 months) and 4/8 weeks past surgery. µCT-analysis for assessing epiphyseal bone architecture was performed as a longitudinal study at 4/8 weeks after OA-induction. Collagen II, ICAM-1 and MC1 expression was analysed by immunohistochemistry. Mc1re/e mice display less Safranin O and collagen II stained articular cartilage area compared to WT prior to OA-induction without signs of spontaneous cartilage surface erosion. This MC1-signaling deficiency related cartilage phenotype persisted in 6 month animals. At 4/8 weeks after OA-induction cartilage erosions were increased in Mc1re/e knees paralleled by weaker collagen II staining. Prior to OA-induction, Mc1re/e mice do not differ from WT with respect to bone parameters. During OA, Mc1re/e mice developed more osteophytes and had higher epiphyseal bone density and mass. Trabecular thickness was increased while concomitantly trabecular separation was decreased in Mc1re/e mice. Numbers of ICAM-positive chondrocytes were equal in non-operated 11 weeks Mc1re/e and WT whereas number of positive chondrocytes decreased during OA-progression. Unchallenged Mc1re/e mice display smaller articular cartilage covered area without OA-related surface erosions indicating that MC1-signaling is critical for proper cartilage matrix integrity and formation. When challenged with OA, Mc1re/e mice develop a more severe OA-pathology. Our data suggest that MC1-signaling protects against cartilage degradation and subchondral bone sclerosis in OA indicating a beneficial role of the POMC system in joint pathophysiology.

Melanocortin 1 Receptor-Signaling Deficiency Results in an Articular Cartilage Phenotype and Accelerates Pathogenesis of Surgically Induced Murine Osteoarthritis

PubMed Central

Hackmayer, Gerit; Greth, Carina; Bauer, Richard J.; Kleinschmidt, Kerstin; Bettenworth, Dominik; Böhm, Markus; Grifka, Joachim; Grässel, Susanne

2014-01-01

Proopiomelanocortin-derived peptides exert pleiotropic effects via binding to melanocortin receptors (MCR). MCR-subtypes have been detected in cartilage and bone and mediate an increasing number of effects in diathrodial joints. This study aims to determine the role of MC1-receptors (MC1) in joint physiology and pathogenesis of osteoarthritis (OA) using MC1-signaling deficient mice (Mc1re/e). OA was surgically induced in Mc1re/e and wild-type (WT) mice by transection of the medial meniscotibial ligament. Histomorphometry of Safranin O stained articular cartilage was performed with non-operated controls (11 weeks and 6 months) and 4/8 weeks past surgery. µCT–analysis for assessing epiphyseal bone architecture was performed as a longitudinal study at 4/8 weeks after OA-induction. Collagen II, ICAM-1 and MC1 expression was analysed by immunohistochemistry. Mc1re/e mice display less Safranin O and collagen II stained articular cartilage area compared to WT prior to OA-induction without signs of spontaneous cartilage surface erosion. This MC1-signaling deficiency related cartilage phenotype persisted in 6 month animals. At 4/8 weeks after OA-induction cartilage erosions were increased in Mc1re/e knees paralleled by weaker collagen II staining. Prior to OA-induction, Mc1re/e mice do not differ from WT with respect to bone parameters. During OA, Mc1re/e mice developed more osteophytes and had higher epiphyseal bone density and mass. Trabecular thickness was increased while concomitantly trabecular separation was decreased in Mc1re/e mice. Numbers of ICAM-positive chondrocytes were equal in non-operated 11 weeks Mc1re/e and WT whereas number of positive chondrocytes decreased during OA-progression. Unchallenged Mc1re/e mice display smaller articular cartilage covered area without OA-related surface erosions indicating that MC1-signaling is critical for proper cartilage matrix integrity and formation. When challenged with OA, Mc1re/e mice develop a more severe OA-pathology. Our data suggest that MC1-signaling protects against cartilage degradation and subchondral bone sclerosis in OA indicating a beneficial role of the POMC system in joint pathophysiology. PMID:25191747

Intra-Prostate Cancer Vaccine Inducer

DTIC Science & Technology

2006-07-01

4 that RNAi technology is possibly a more effective and reliable method to silence expression of a given gene. Therefore, we constructed an Ii...experiments, bone marrow cells were extracted from the femurs of BALB/c mice. Cells were plated at 4x106 cells in 100 mm dishes, in RPMI 1640-medium...permeabilized with saponin in preparation for staining with Ii monoclonal antibodies (data not shown). C1 E1 C2 E2 Figure 3 (C1) represents flow cytometric

Congenital Stapes Ankylosis in Children: Surgical Findings and Results in 35 Cases.

PubMed

Vincent, Robert; Wegner, Inge; Kamalski, Digna M A; Bittermann, Arnold J N; Grolman, Wilko

2016-04-01

To evaluate surgical findings and hearing results in children undergoing middle ear surgery for congenital stapes ankylosis with or without other ossicular malformations (Teunissen and Cremers class I and class II malformations). A nonrandomized, nonblinded case series of prospectively collected data. A tertiary referral center. Twenty-eight consecutive pediatric patients who underwent 35 surgical procedures for congenital stapes ankylosis with or without other ossicular malformations and had available postoperative pure-tone audiometry. Primary stapedotomy with vein graft interposition and reconstruction with a Teflon piston, bucket handle prosthesis or total ossicular replacement prosthesis. Pre- and postoperative audiometric evaluation using four-frequency (0.5, 1, 2, and 4 kHz) audiometry. Air-conduction thresholds, bone-conduction thresholds, and air-bone gaps (ABGs) were measured. Postoperative audiometry was performed at 3, 6, 9, 12, 18, and 24 months after surgery and at a yearly interval thereafter. Overall, a postoperative ABG closure of 10 dB or less was achieved in 73% of class I cases and in 50% of class II cases. A postoperative ABG closure of 20 dB or less was achieved in 77% of class I cases and 67% of class II cases. Postoperative sensorineural hearing loss occurred in one class I case (4%) and none of the class II cases. Stapedotomy is a safe and feasible treatment option in children with congenital stapes ankylosis.

Surgical correction of bilateral metacarpophalangeal valgus with curved osteotomies and type II external skeletal fixation in a seven-month-old alpaca.

PubMed

Schoonover, Mike J; Whitfield, Chase T; Rochat, Mark C; Streeter, Robert N; Sippel, Kate

2016-09-20

To report the successful surgical correction of severe bilateral metacarpophalangeal valgus angular limb deformities in a seven-month-old intact male alpaca cria using curved osteotomies stabilized with type II external skeletal fixation. Using a 21 mm crescentic shaped oscillating saw blade, bilateral osteotomies were performed in the distal metaphyses of the fused third and fourth metacarpal bones to correct valgus angular limb deformity of the metacarpophalangeal joints. Axial alignment of each limb was achieved by medially rotating the distal metacarpus in the frontal plane along the curved osteotomies. The osteotomies were stabilized using type II external skeletal fixators. The alpaca was immediately weight-bearing following the surgical procedure and no to minimal lameness was observed during healing of the osteotomies. Evaluation at five and 10 months following the surgery demonstrated acceptable axial alignment in the left forelimb while moderate to severe varus deformity (overcorrection) was observed in the right. Curved osteotomy of the distal metacarpus stabilized with type II external skeletal fixation can provide a favourable outcome in older alpaca crias affected with metacarpophalangeal angular limb deformities. Placement of the distal transfixation pins relative to the metacarpal physes should be carefully evaluated as overcorrection is possible, especially if growthpotential remains in only one physis of the fused third and fourth metacarpal bones.

Alternatives to Autologous Bone Graft in Alveolar Cleft Reconstruction: The State of Alveolar Tissue Engineering.

PubMed

Liang, Fan; Leland, Hyuma; Jedrzejewski, Breanna; Auslander, Allyn; Maniskas, Seija; Swanson, Jordan; Urata, Mark; Hammoudeh, Jeffrey; Magee, William

2018-05-01

Alveolar cleft reconstruction has historically relied on autologous iliac crest bone grafting (ICBG), but donor site morbidity, pain, and prolonged hospitalization have prompted the search for bone graft substitutes. The authors evaluated bone graft substitutes with the highest levels of evidence, and highlight the products that show promise in alveolar cleft repair and in maxillary augmentation. This comprehensive review guides the craniofacial surgeon toward safe and informed utilization of biomaterials in the alveolar cleft.A literature search was performed to identify in vitro human studies that fulfilled the following criteria: Level I or Level II of evidence, ≥30 subjects, and a direct comparison between a autologous bone graft and a bone graft substitute. A second literature search was performed that captured all studies, regardless of level of evidence, which evaluated bone graft substitutes for alveolar cleft repair or alveolar augmentation for dental implants. Adverse events for each of these products were tabulated as well.Sixteen studies featuring 6 bone graft substitutes: hydroxyapatite, demineralized bone matrix (DBM), β-tricalcium phosphate (TCP), calcium phosphate, recombinant human bone morphogenic protein-2 (rhBMP-2), and rhBMP7 fit the inclusion criteria for the first search. Through our second search, the authors found that DBM, TCP, rhBMP-2, and rhBMP7 have been studied most extensively in the alveolar cleft literature, though frequently in studies using less rigorous methodology (Level III evidence or below). rhBMP-2 was the best studied and showed comparable efficacy to ICBG in terms of volume of bone regeneration, bone density, and capacity to accommodate tooth eruption within the graft site. Pricing for products ranged from $290 to $3110 per 5 mL.The balance between innovation and safety is a complex process requiring constant vigilance and evaluation. Here, the authors profile several bone graft substitutes that demonstrate the most promise in alveolar cleft reconstruction.

Mathematical evaluation of the influence of multiple factors on implant stability quotient values in clinical practice: a retrospective study

PubMed Central

Huang, Hairong; Wismeijer, Daniel; Shao, Xianhong; Wu, Gang

2016-01-01

Objectives The objective of this study is to mathematically evaluate the influence of multiple factors on implant stability quotient values in clinical practice. Patients and methods Resonance frequency analysis was performed at T1 (measured immediately at the time of implant placement) and at T2 (measured before dental restoration) in 177 patients (329 implants). Using a multivariate linear regression model, we analyzed the influence of the following eleven candidate factors: sex, age, maxillary/mandibular location, bone type, immediate/delayed implantation, bone grafting (presence or absence), insertion torque, I-/II-stage healing pattern, implant diameter, implant length, and T1–T2 time interval. Results The following factors were identified to significantly influence the implant stability quotient (ISQ) values at T1: insertion torque, bone grafting, I-/II-stage healing pattern, immediate/delayed implantation, maxillary/mandibular location, implant diameter, and sex. In contrast, the ISQ values at T2 were significantly influenced only by three factors: implant diameter, T1–T2 time interval, and insertion torque. Conclusion Among the eleven candidate factors, seven key factors were found to influence the T1-ISQ values, while only three key factors influenced the T2-ISQ values. Both T1 and T2-ISQ values were found to be influenced by implant diameter and insertion torque. T1 was influenced specifically by the sex of the patient, the location (maxillary or mandibular), the implantation mode (immediate/delayed implantation), the healing stage, and the absence or presence of bone graft materials. PMID:27785040

Elastic fiber-mediated enthesis in the human middle ear.

PubMed

Kawase, Tetsuaki; Shibata, Shunichi; Katori, Yukio; Ohtsuka, Aiji; Murakami, Gen; Fujimiya, Mineko

2012-10-01

Adaptation to constant vibration (acoustic oscillation) is likely to confer a specific morphology at the bone-tendon and bone-ligament interfaces at the ear ossicles, which therefore represent an exciting target of enthesis research. We histologically examined (i) the bone attachments of the tensor tympani and stapedius muscles and (ii) the annular ligament of the incudostapedial joint obtained from seven elderly donated cadavers. Notably, both aldehyde-fuchsin and elastic-Masson staining demonstrated that the major fibrous component of the entheses was not collagen fibers but mature elastic fibers. The positive controls for elastic fiber staining were the arterial wall elastic laminae included in the temporal bone materials. The elastic fibers were inserted deeply into the type II collagen-poor fibrocartilage covering the ear ossicles. The muscle tendons were composed of an outer thin layer of collagen fibers and an inner thick core of elastic fibers near the malleus or stapes. In the unique elastic fiber-mediated entheses, hyaluronan, versican and fibronectin were expressed strongly along the elastic fibers. The hyaluronan seemed to act as a friction-reducing lubricant for the elastic fibers. Aggrecan was labeled strongly in a disk- or plica-like fibrous mass on the inner side of the elastic fiber-rich ligament, possibly due to compression stress from the ligament. Tenascin-c was not evident in the entheses. The elastic fiber-mediated entheses appeared resistant to tissue destruction in an environment exposed to constant vibration. The morphology was unlikely to be the result of age-related degeneration. © 2012 The Authors Journal of Anatomy © 2012 Anatomical Society.

The in vivo performance of a sol-gel glass and a glass-ceramic in the treatment of limited bone defects.

PubMed

Gil-Albarova, Jorge; Garrido-Lahiguera, Ruth; Salinas, Antonio J; Román, Jesús; Bueno-Lozano, Antonio L; Gil-Albarova, Raúl; Vallet-Regí, María

2004-08-01

The in vivo evaluation, in New Zealand rabbits, of a SiO(2)-P(2)O(5)-CaO sol-gel glass and a SiO(2)-P(2)O(5)-CaO-MgO glass-ceramic, both bioactive in Kokubo's simulated body fluid (SBF), is presented. Bone defects, performed in the lateral aspect of distal right femoral epiphysis, 5mm in diameter and 4mm in depth, were filled with (i) sol-gel glass disks, (ii) glass-ceramic disks, or (iii) no material (control group). Each group included 8 mature and 8 immature rabbits. A 4-month radiographic study showed good implant stability without axial deviation of extremities in immature animals and periosteal growth and remodelling around and over the bone defect. After sacrifice, the macroscopic study showed healing of bone defects, with bone coating over the implants. The morphometric study showed a more generous bone formation in animals receiving sol-gel glass or glass-ceramic disks than in control group. Histomorphometric study showed an intimate union of the new-formed bone to the implants. This study allows considering both materials as eligible for bone substitution or repair. Their indications could include cavities filling and the coating of implant surfaces. The minimum degradation of glass-ceramic disks suggests its application in locations of load or transmission forces. As specific indication in growth plate surgery, both materials could be used as material of interposition after bony bridges resection.

Hard tissue alterations after socket preservation with additional buccal overbuilding: a study in the beagle dog.

PubMed

Fickl, Stefan; Zuhr, Otto; Wachtel, Hannes; Kebschull, Moritz; Hürzeler, Markus B

2009-10-01

The aim of this study was to histometrically assess alterations of the ridge following socket preservation alone and socket preservation with additional buccal overbuilding. In five beagle dogs four extraction sites were randomly subjected to one of the following treatments: Tx 1: The socket was filled with BioOss Collagen and covered with a free gingival graft from the palate. Tx 2: The buccal bone plate was augmented using the GBR-technique, the socket was filled with BioOss Collagen and covered with a free gingival graft. Tx 3: The buccal bone plate was forced into a buccal direction using a manual bone spreader. The socket was filled with BioOss Collagen and covered with a free gingival graft from the palate. Tx 4: The socket was filled with BioOss Collagen and a combined free gingival/connective tissue graft was used to cover the socket and for buccal tissue augmentation. For each experimental site, two histological sections were subjected to histometric analysis and evaluated for (i) vertical bone dimensions and (ii) horizontal bone dimensions. All treatment groups showed horizontal and vertical bone loss. The mean vertical bone loss of the buccal bone plate was significantly lower in Tx 4 than in the other groups, while no statistical significant differences could be detected among the groups in the horizontal dimension. Overbuilding the buccal aspect in combination with socket preservation does not seem to be a suitable technique to compensate for the alterations after tooth extraction.

Bone marrow stimulation of the medial femoral condyle produces inferior cartilage and bone repair compared to the trochlea in a rabbit surgical model.

PubMed

Chen, Hongmei; Chevrier, Anik; Hoemann, Caroline D; Sun, Jun; Picard, Genevieve; Buschmann, Michael D

2013-11-01

The influence of the location of cartilage lesions on cartilage repair outcome is incompletely understood. This study compared cartilage and bone repair in medial femoral condylar (MFC) versus femoral trochlear (TR) defects 3 months after bone marrow stimulation in mature rabbits. Intact femurs from adult rabbits served as controls. Results from quantitative histomorphometry and histological scoring showed that bone marrow stimulation produced inferior soft tissue repair in MFC versus TR defects, as indicated by significantly lower % Fill (p = 0.03), a significant increase in collagen type I immunostaining (p < 0.00001) and lower O'Driscoll scores (p < 0.05). 3D micro-CT analysis showed that repaired TR defects regained normal un-operated values of bone volume fraction, trabecular thickness, and trabecular number, whereas in MFC defects the repaired bone architecture appeared immature and less dense compared to intact un-operated MFC controls (p < 0.0001). Severe medial meniscal damage was found in 28% of operated animals and was strongly correlated with (i) low cartilage defect fill, (ii) incomplete bone repair in MFC, and (iii) with a more posterior defect placement in the weight-bearing region. We conclude that the location of cartilage lesions influences cartilage repair, with better outcome in TR versus MFC defects in rabbits. Meniscal degeneration is associated with cartilage damage. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Low Bone Mineral Content and Challenges in Interpretation of Dual-Energy X-Ray Absorptiometry in Children With Mucopolysaccharidosis Types I, II, and VI

PubMed Central

Polgreen, Lynda E.; Thomas, William; Fung, Ellen; Viskochil, David; Stevenson, David A.; Steinberger, Julia; Orchard, Paul; Whitley, Chester B.; Ensrud, Kristine E.

2013-01-01

Osteoporosis has been described in animal models of mucopolysaccharidosis (MPS). Whether clinically significant osteoporosis is common among children with MPS is unknown. Therefore, cross-sectional data from whole body (WB; excluding head) and lumbar spine (LS) bone mineral density (BMD) compared with sex-, chronologic age–, and ethnicity-matched healthy individuals (Zage), height-for-age (HAZ) Z-score (ZHAZ) and bone mineral content (BMC) measured by dual-energy X-ray absorptiometry (DXA) in 40 children with MPS were analyzed. A subset of these children (n = 24) was matched 1:3 by age and sex to a group of healthy children (n = 72) for comparison of BMC adjusted for Tanner stage, race, lean body mass, height, and bone area. Low BMD Z-score was defined as Z-score of −2 or less. In children with MPS, 15% had low WB Zage and 48% had low LS Zage; 0% and 6% had low WB ZHAZ and low LS ZHAZ, respectively. Adjusted WB BMC was lower in MPS participants (p = 0.009). In conclusion, children with MPS had deficits in WB BMC after adjustments for stature and bone area. HAZ adjustment underestimated bone deficits (i.e., overestimated WB BMD Z-scores) in children with MPS likely owing to their abnormal bone shape. The influence of severe short stature and bone geometry on DXA measurements must be considered in children with MPS to avoid unnecessary exposure to antiresorptive treatments. PMID:23562131

Effect of a novel load-bearing trabecular Nitinol scaffold on rabbit radius bone regeneration

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

Gotman, Irena, E-mail: gotman@technion.ac.il; Gutmanas, Elazar Y., E-mail: gutmanas@technion.ac.il; National Research Tomsk Polytechnic University, Tomsk, 634050

The research aim was to evaluate the bone regeneration capability of novel load-bearing NiTi alloy (Nitinol) scaffolds in a critical-size defect (CSD) model. High strength “trabecular Nitinol” scaffolds were prepared by PIRAC (Powder Immersion Reaction Assisted Coating) annealing of the highly porous Ni foam in Ti powder at 900°C. This was followed by PIRAC nitriding to mitigate the release of potentially toxic Ni ions. Scaffolds phase composition and microstructure were characterized by X-ray diffraction and scanning electron microscopy (SEM/EDS), and their mechanical properties were tested in compression. New Zealand white rabbits received bone defect in right radius and were dividedmore » in four groups randomly. In the control group, nothing was placed in the defect. In other groups, NiTi scaffolds were implanted in the defect: (i) as produced, (ii) loaded with bone marrow aspirate (BMA), and (iii) biomimetically CaP-coated. The animals were sacrificed after 12 weeks. The forelimbs with scaffolds were resected, fixed, sectioned and examined in SEM. New bone formation inside the scaffold was studied by EDS analysis and by the processing of backscattered electron images. Bone ingrowth into the scaffold was observed in all implant groups, mostly next to the ulna. New bone formation was strongly enhanced by BMA loading and biomimeatic CaP coating, the bone penetrating as much as 1–1.5 mm into the scaffold. The results of this preliminary study demonstrate that the newly developed high strength trabecular Nitinol scaffolds can be successfully used for bone regeneration in critical size defects.« less

In Silico Investigations of the Anti-Catabolic Effects of Pamidronate and Denosumab on Multiple Myeloma-Induced Bone Disease

PubMed Central

Wang, Yan; Lin, Bo

2012-01-01

It is unclear whether the new anti-catabolic agent denosumab represents a viable alternative to the widely used anti-catabolic agent pamidronate in the treatment of Multiple Myeloma (MM)-induced bone disease. This lack of clarity primarily stems from the lack of sufficient clinical investigations, which are costly and time consuming. However, in silico investigations require less time and expense, suggesting that they may be a useful complement to traditional clinical investigations. In this paper, we aim to (i) develop integrated computational models that are suitable for investigating the effects of pamidronate and denosumab on MM-induced bone disease and (ii) evaluate the responses to pamidronate and denosumab treatments using these integrated models. To achieve these goals, pharmacokinetic models of pamidronate and denosumab are first developed and then calibrated and validated using different clinical datasets. Next, the integrated computational models are developed by incorporating the simulated transient concentrations of pamidronate and denosumab and simulations of their actions on the MM-bone compartment into the previously proposed MM-bone model. These integrated models are further calibrated and validated by different clinical datasets so that they are suitable to be applied to investigate the responses to the pamidronate and denosumab treatments. Finally, these responses are evaluated by quantifying the bone volume, bone turnover, and MM-cell density. This evaluation identifies four denosumab regimes that potentially produce an overall improved bone-related response compared with the recommended pamidronate regime. This in silico investigation supports the idea that denosumab represents an appropriate alternative to pamidronate in the treatment of MM-induced bone disease. PMID:23028650

Comparison of naturally occurring and ligature-induced peri-implantitis bone defects in humans and dogs.

PubMed

Schwarz, Frank; Herten, Monika; Sager, Martin; Bieling, Katrin; Sculean, Anton; Becker, Jürgen

2007-04-01

The aim of the present study was to evaluate and compare naturally occuring and ligature-induced peri-implantitis bone defects in humans and dogs. Twenty-four partially and fully edentulous patients undergoing peri-implant bone augmentation procedures due to advanced peri-implant infections were included in this study (n=40 implants). Furthermore, peri-implantitis was induced by ligature placement and plaque accumulation in five beagle dogs for three months following implant insertion (n=15 implants). The ligatures were removed when about 30% of the initial bone was lost. During open flap surgery, configuration and defect characteristics of the peri-implant bone loss were recorded in both humans and dogs. Open flap surgery generally revealed two different classes of peri-implant bone defects. While Class I defects featured well-defined intrabony components, Class II defects were characterized by consistent horizontal bone loss. The allocation of intrabony components of Class I defects regarding the implant body allowed a subdivision of five different configurations (Classes Ia-e). In particular, human defects were most frequently Class Ie (55.3%), followed by Ib (15.8%), Ic (13.3%), Id (10.2%), and Ia (5.4%). Similarly, bone defects in dogs were also most frequently Class Ie (86.6%), while merely two out of 15 defects were Classes Ia and Ic (6.7%, respectively). Within the limits of the present study, it might be concluded that configurations and sizes of ligature-induced peri-implantitis bone defects in dogs seemed to resemble naturally occurring lesions in humans.

Effect of socket grafting with deproteinized bone mineral: An RCT on dimensional alterations after 6 months.

PubMed

Tomasi, Cristiano; Donati, Mauro; Cecchinato, Denis; Szathvary, Isacco; Corrà, Enrico; Lindhe, Jan

2018-05-01

To examine if (i) characteristics of the fresh extraction socket site influenced subsequent dimensional alterations and (ii) placement of deproteinized bovine mineral in the socket affected volumetric change during healing. Twenty seven subjects and 28 extraction sites were included. Immediately after the removal of the tooth and after 6 months of healing, stone and virtual models of the jaw were produced. A cone beam computerized tomography scan was obtained immediately after extraction and the thickness of the buccal bone wall at the extraction site was measured. Extraction sites were randomly assigned to test or control group. In the test group, extraction sockets were filled with deproteinized bone mineral and covered with a collagen membrane. In the control group, only a collagen membrane was placed. The thickness of the buccal bone wall at the extraction site influenced the amount of volume reduction that occurred. Socket grafting influenced the degree of ridge diminution only at sites where the buccal bone wall was thin (≤ 1 mm). A graft comprised of collagen-enriched deproteinized bovine bone mineral, placed to fill extraction sockets failed to influence the overall diminution of the ridge that occurred during healing. The thickness of the buccal bone wall apparently had a significant influence on volumetric alterations of the edentulous ridge following tooth extraction. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Immunolocalization of matrix metalloproteinase-13 on bone surface under osteoclasts in rat tibia.

PubMed

Nakamura, Hiroaki; Sato, Ginga; Hirata, Azumi; Yamamoto, Toshio

2004-01-01

Matrix metalloproteinase (MMP)-13 (an interstitial collagenase also called collagenase 3) is involved in degradation of extracellular matrix in various tissues. Using immunohistochemistry and Western blotting, we investigated localization of MMP-13 in rat tibia, to clarify the role of MMP-13 in bone resorption. MMP-13 reactivity was mainly seen on bone surfaces under osteoclasts, and in some osteocytes and their lacunae near osteoclasts. However, immunoreactivity was not seen in chondrocytes or osteoclasts. MMP-13 was also localized on cement lines in the epiphysis. In the growth plate erosion zone, perivascular cells showed MMP-13 reactivity. Immunoelectron microscopy revealed that MMP-13 was localized on the bone surfaces, under the ruffled borders and some clear zones of osteoclasts. Gold-labeled MMP-13 was closely associated with collagen fibrils. Gold labeling was also detected in Golgi apparatus of osteocytes adjacent to osteoclasts and bone lining cells. Western blotting showed that MMP-13 was mainly associated with mineralized bone matrix. These findings suggest that MMP-13 synthesized and secreted by osteoblast-lineage cells is localized under the ruffled borders of osteoclasts. MMP-13 may play an important role in degradation of type I collagen in bone matrix, acting in concert with cathepsin K and MMP-9 produced by osteoclasts. MMP-13 in perivascular cells may be involved in removal of cartilage matrix proteins such as type II collagen and aggrecan.

Novel antiosteoclastogenic activity of phloretin antagonizing RANKL-induced osteoclast differentiation of murine macrophages.

PubMed

Kim, Jung-Lye; Kang, Min-Kyung; Gong, Ju-Hyun; Park, Sin-Hye; Han, Seon-Young; Kang, Young-Hee

2012-08-01

Bone-remodeling imbalance resulting in more bone resorption than bone formation is known to cause skeletal diseases such as osteoporosis. Phloretin, a natural dihydrochalcone compound largely present in apple peels, possesses antiphotoaging, and antiinflammatory activity. Phloretin inhibited receptor activator of NF-κB ligand (RANKL)-induced formation of multinucleated osteoclasts and diminished bone resorption area produced during the osteoclast differentiation process. It was also found that ≥ 10 μM phloretin reduced RANKL-enhanced tartrate-resistance acid phosphatase activity and matrix metalloproteinase-9 secretion in a dose-dependent manner. The phloretin treatment retarded RANKL-induced expression of carbonic anhydrase II, vacuolar-type H(+) -ATPase D2 and β3 integrin, all involved in the bone resorption. Furthermore, submicromolar phloretin diminished the expression and secretion of cathepsin K elevated by RANKL, being concurrent with inhibition of TRAF6 induction and NF-κB activation. RANKL-induced activation of nuclear factor of activated T cells c1 (NFATc1) and microphthalmia-associated transcription factor was also suppressed by phloretin. These results demonstrate that the inhibition of osteoclast differentiation and bone resorption by phloretin entail a disturbance of TRAF6-NFATc1-NF-κB pathway triggered by RANKL. Therefore, phloretin may be a potential therapeutic agent targeting osteoclast differentiation and bone resorption in skeletal diseases such as osteoporosis. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Treatment effects of magnetic Twin-block appliance for class II cases].

PubMed

Wu, Jian-Yong; Liu, Jian; Li, Qi-Shun; Xu, Tian-Min; Lin, Jiu-Xiang

2007-09-01

To evaluate the effects of magnetic Twin-block appliance in the treatment of skeletal class II cases. The magnetic Twin-block appliance was embedded with two pairs of neodymium-iron-boron (Nd(2)Fe(14)B) rare earth permanent magnets in the upper and lower inclined planes of Twin-block appliance. The sample comprised of 13 skeletal class II patients in the late mixed or early permanent dentition treated by magnetic Twin-block appliance. Cephalometric films were taken before and after treatment. Helix CT images of the temporomandibular joint (TMJ) in all patients were examined before treatment (T1), during treatment (4 months after appliance placement, T2), after treatment (T3) and one year after treatment (T4). A double contour image was detected in the superior posterior part of the condylar head on the pseudo-sagittal reconstruction plane pictures of T2 in 11 patients. The double contour image could be observed in most patients as well. This image also exhibited on the pictures of T3 in several patients. On the pictures of T2 and T3 in some patients, interruption of cortical bone and "bifurcation phenomenon" of condyles were shown. Pictures of T1 and T4 were similar and no signs of remodeling of TMJ were observed. Cephalometric analysis revealed significant changes in the maxillofacial structure after treatment. The profile of patients improved. Bone remodeling of condyle occurred during the magnetic Twin-block treatment in class II patients. Magnetic Twin-block appliance was effective in the treatment of the growing skeletal class II patients.

The minimum follow-up required for radial head arthroplasty: a meta-analysis.

PubMed

Laumonerie, P; Reina, N; Kerezoudis, P; Declaux, S; Tibbo, M E; Bonnevialle, N; Mansat, P

2017-12-01

The primary aim of this study was to define the standard minimum follow-up required to produce a reliable estimate of the rate of re-operation after radial head arthroplasty (RHA). The secondary objective was to define the leading reasons for re-operation. Four electronic databases, between January 2000 and March 2017 were searched. Articles reporting reasons for re-operation (Group I) and results (Group II) after RHA were included. In Group I, a meta-analysis was performed to obtain the standard minimum follow-up, the mean time to re-operation and the reason for failure. In Group II, the minimum follow-up for each study was compared with the standard minimum follow-up. A total of 40 studies were analysed: three were Group I and included 80 implants and 37 were Group II and included 1192 implants. In Group I, the mean time to re-operation was 1.37 years (0 to 11.25), the standard minimum follow-up was 3.25 years; painful loosening was the main indication for re-operation. In Group II, 33 Group II articles (89.2%) reported a minimum follow-up of < 3.25 years. The literature does not provide a reliable estimate of the rate of re-operation after RHA. The reproducibility of results would be improved by using a minimum follow-up of three years combined with a consensus of the definition of the reasons for failure after RHA. Cite this article: Bone Joint J 2017;99-B:1561-70. ©2017 The British Editorial Society of Bone & Joint Surgery.

Effect of recombinant insulin-like growth factor-1 treatment on short-term linear growth in a child with Majewski osteodysplastic primordial dwarfism type II and hepatic insufficiency.

PubMed

Faienza, Maria Felicia; Acquafredda, Angelo; D'Aniello, Mariangela; Soldano, Lucia; Marzano, Flaviana; Ventura, Annamaria; Cavallo, Luciano

2013-01-01

We report the case of a boy affected by severe intrauterine and postnatal growth retardation, microcephaly, facial dysmorphisms and postnecrotic cirrhosis, diagnosed at birth as having Seckel syndrome, and subsequently confirmed as Majewski osteodysplastic primordial dwarfism type II (MOPD II) on the basis of clinical and radiological features of skeletal dysplasia. At our observation (6 years 7 months) he presented height -10.3 standard deviation score (SDS), weight -22.1 SDS, head circumference -8 SDS, delayed bone age of 4 years with respect to chronological age. In consideration of the low levels of insulin-like growth factor-1 (IGF-1) as well as of hepatic insufficiency, we started the treatment with recombinant human IGF-1 (rhIGF-1) at the dose of 0.04 mg/kg in 2 doses/day, with an increase of 0.04 mg/kg after 1 week until the maximum dose of 0.12 mg/kg. We observed an early response to rhIGF-1 treatment, with a shift of height velocity from 1.8 cm/year (-4.6 SDS) at 4 cm/year (-1.9 SDS), and an increase in bone age of 1.5 years during the first 6 months. rhIGF-1 treatment does not seem to be able to replace the physiological action of IGF-1 in patients with MOPD II and hepatic insufficiency, however, it seems to preserve the typical growth pattern of MOPD II patients, avoiding a further widening of the growth deficiency in these subjects.

Horizontal alveolar bone loss: A periodontal orphan

PubMed Central

Jayakumar, A.; Rohini, S.; Naveen, A.; Haritha, A.; Reddy, Krishnanjeneya

2010-01-01

Background: Attempts to successfully regenerate lost alveolar bone have always been a clinician’s dream. Angular defects, at least, have a fairer chance, but the same cannot be said about horizontal bone loss. The purpose of the present study was to evaluate the prevalence of horizontal alveolar bone loss and vertical bone defects in periodontal patients; and later, to correlate it with the treatment modalities available in the literature for horizontal and vertical bone defects. Materials and Methods: The study was conducted in two parts. Part I was the radiographic evaluation of 150 orthopantomographs (OPGs) (of patients diagnosed with chronic periodontitis and seeking periodontal care), which were digitized and read using the AutoCAD 2006 software. All the periodontitis-affected teeth were categorized as teeth with vertical defects (if the defect angle was ≤45° and defect depth was ≥3 mm) or as having horizontal bone loss. Part II of the study comprised search of the literature on treatment modalities for horizontal and vertical bone loss in four selected periodontal journals. Results: Out of the 150 OPGs studied, 54 (36%) OPGs showed one or more vertical defects. Totally, 3,371 teeth were studied, out of which horizontal bone loss was found in 3,107 (92.2%) teeth, and vertical defects were found only in 264 (7.8%) of the teeth, which was statistically significant (P<.001). Search of the selected journals revealed 477 papers have addressed the treatment modalities for vertical and horizontal types of bone loss specifically. Out of the 477 papers, 461 (96.3%) have addressed vertical bone loss, and 18 (3.7%) have addressed treatment options for horizontal bone loss. Two papers have addressed both types of bone loss and are included in both categories. Conclusion: Horizontal bone loss is more prevalent than vertical bone loss but has been sidelined by researchers as very few papers have been published on the subject of regenerative treatment modalities for this type of bone loss. This study should be an impetus for greater attention to an otherwise ubiquitous periodontal challenge. PMID:21760673

High glucose induces bone marrow-derived mesenchymal stem cell senescence by upregulating autophagy.

PubMed

Chang, Tzu-Ching; Hsu, Min-Fen; Wu, Kenneth K

2015-01-01

Hyperglycemia was reported to cause bone marrow hematopoietic niche dysfunction, and high glucose (HG) in the cultured medium induces MSC senescence. The underlying mechanism is unclear. Here, we investigated the role of HG-induced autophagy in bone-marrow-derived mesenchymal stem cell (BMSC) senescence. HG (25 mM) increased expression of Beclin-1, Atg 5, 7 and 12, generation of LC3-II and autophagosome formation which was correlated with development of cell senescence. Pretreatment of HG-MSC with 3-methyladenine (3-MA) prevented senescence but increased apoptosis. N-acetylcysteine (NAC) was effective in abrogating HG-induced autophagy accompanied by prevention of senescence. Diphenyleneiodonium (DPI), an inhibitor of NADPH oxidase, blocked autophagy and senescence in a manner comparable to NAC. 3-MA, NAC and DPI inhibited HG-induced interleukin-6 production in BMSCs. These results suggest that hyperglycemia induces MSC senescence and local inflammation via a novel oxidant-mediated autophagy which contributes to bone marrow niche dysfunction and hematopoietic impairment.

Fat embolism syndrome after nailing an isolated open tibial fracture in a stable patient: a case report.

PubMed

Aparicio, Gustavo; Soler, Isabel; López-Durán, Luis

2014-04-14

Fat embolism syndrome is a potentially fatal complication of long bone fractures. It is usually seen in the context of polytrauma or a femoral fracture. There are few reports of fat embolism syndrome occurring after isolated long bone fractures other than those of the femur. We describe a case of fat embolism syndrome in a 33-year-old Caucasian man. He was being seen for an isolated Gustilo's grade II open tibial fracture. He was deemed clinically stable, so we proceeded to treat the fracture with intramedullary reamed nailing. He developed fat embolism syndrome intraoperatively and was treated successfully. This case caused us to question the use of injury severity scoring for isolated long bone fractures. It suggests that parameters that have been described in the literature other than that the patient is apparently clinically stable should be used to establish the best time for nailing a long bone fracture, thereby improving patient safety.

Fat embolism syndrome after nailing an isolated open tibial fracture in a stable patient: a case report

PubMed Central

2014-01-01

Background Fat embolism syndrome is a potentially fatal complication of long bone fractures. It is usually seen in the context of polytrauma or a femoral fracture. There are few reports of fat embolism syndrome occurring after isolated long bone fractures other than those of the femur. Case presentation We describe a case of fat embolism syndrome in a 33-year-old Caucasian man. He was being seen for an isolated Gustilo’s grade II open tibial fracture. He was deemed clinically stable, so we proceeded to treat the fracture with intramedullary reamed nailing. He developed fat embolism syndrome intraoperatively and was treated successfully. Conclusion This case caused us to question the use of injury severity scoring for isolated long bone fractures. It suggests that parameters that have been described in the literature other than that the patient is apparently clinically stable should be used to establish the best time for nailing a long bone fracture, thereby improving patient safety. PMID:24731759

Effects of manganese deficiency on serum hormones and biochemical markers of bone metabolism in chicks.

PubMed

Zhaojun, Wang; Lin, Wang; Zhenyong, Wang; Jian, Wang; Ran, Liu

2013-05-01

In order to investigate the effect of manganese (Mn) deficiency on bone metabolism in chicks, ninety 1-day-old male Arbor Acre chicks were randomly divided into 3 groups and each group were given a diet having a different concentration of Mn (60 mg kg(-1), control group; 40 mg kg(-1), Mn-deficient group I; 8.7 mg kg(-1), Mn-deficient group II). The serum was collected at 42 days old. Tests were performed to evaluate the changes in the levels of PTH, CT, ALP, TrACP, HOP TNF-alpha, OC, Mn and Ca in the serum of the chicks and the results showed that the levels of CT, ALP, TrACP, HOP, and Mn decreased markedly (P < 0.05), while PTH, Ca, and TNF-alpha increased markedly (P < 0.05) due to manganese deficiency in the diet, which indicates that Mn deficiency results in disorder of bone regulatory hormones and enzymes of bone metabolism in the serum.

Serum markers of bone turnover are increased by modest weight loss with or without weight-bearing exercise in overweight premenopausal women.

PubMed

Rector, R Scott; Loethen, Joanne; Ruebel, Meghan; Thomas, Tom R; Hinton, Pamela S

2009-10-01

Weight loss improves metabolic fitness and reduces morbidity and mortality; however, weight reduction also reduces bone mineral density (BMD) and increases bone turnover. Weight-bearing aerobic exercise may preserve bone mass and maintain normal bone turnover during weight reduction. We investigated the impact of weight-bearing and nonweight-bearing exercise on serum markers of bone formation and breakdown during short-term, modest weight loss in overweight premenopausal women. Subjects (n = 36) were assigned to 1 of 3 weight-loss interventions designed to produce a 5% reduction in body weight over 6 weeks: (i) energy restriction only (n = 11; DIET); (ii) energy restriction plus nonweight-bearing exercise (n = 12, CYCLE); or (iii) energy restriction plus weight-bearing exercise (n = 13, RUN). Bone turnover markers were measured in serum collected at baseline and after weight loss. All groups achieved a ~5% reduction in body weight (DIET = 5.2%; CYCLE = 5.0%; RUN = 4.7%). Osteocalcin (OC) and C-terminal telopeptide of type I collagen (CTX) increased with weight loss in all 3 groups (p < 0.05), whereas bone alkaline phosphatase was unaltered by the weight-loss interventions. At baseline, OC and CTX were positively correlated (r = 0.36, p = 0.03), but the strength of this association was diminished (r = 0.30, p = 0.06) after weight loss. Modest weight loss, regardless of method, resulted in a significant increase in both OC and CTX. Low-impact, weight-bearing exercise had no effect on serum markers of bone formation or resorption in premenopausal women during weight loss. Future studies that examine the effects of high-impact, weight-bearing activity on bone turnover and BMD during weight loss are warranted.

Metabolic Bone Disease in the Context of Metastatic Neuroendocrine Tumor: Differentiation from Skeletal Metastasis, the Molecular PET-CT Imaging Features, and Exploring the Possible Etiopathologies Including Parathyroid Adenoma (MEN1) and Paraneoplastic Humoral Hypercalcemia of Malignancy Due to PTHrP Hypersecretion.

PubMed

Ranade, Rohit; Basu, Sandip

2017-01-01

Three cases of metabolic bone disease in the setting of metastatic neuroendocrine tumor (NET) are illustrated with associated etiopathologies.  One of these cases harbored mixed lesions in the form of vertebral metastasis (biopsy proven) while the other skeletal lesions were caused due to metabolic bone disease related to multiple parathyroid adenomas. While the metastatic lesion was positive on 68Ga-DOTATATE positron emission tomography-computed tomography (PET-CT), the lesions of metabolic bone disease were negative and the 18F-fluoride PET-CT demonstrated the features of metabolic bone scan. Similar picture of metabolic bone disease [18-sodium fluoride (18NaF)/68Ga-DOTATATE mismatch] was documented in the other two patients, while fluorodeoxyglucose (FDG)-PET-CT was variably positive, primarily showing tracer uptake in the metabolic skeletal lesions of the patient with hypersecretion of parathyroid hormone-related protein (PTHrP) by the underlying tumor. Discordance between 18NaF PET-CT and 68Ga-DOTATATE PET-CT serves as a good marker for identification of metabolic bone disease and diagnosing such a clinical entity. In a patient of NET with metabolic bone disease and hypercalcemia, thus, two causes need to be considered: (i) Coexisting parathyroid adenoma in multiple endocrine neoplasia type I (MEN-I) syndrome and (ii) humoral hypercalcemia of malignancy (HHM) related to hypersecretion of PTHrP by the tumor. The correct diagnosis of metabolic bone disease in metastatic NET can alter the management substantially. Interestingly, peptide receptor radionuclide therapy (PRRT) can emerge as a very promising treatment modality in patients of metabolic bone disease caused by HHM in the setting of NET.

Drilling force and temperature of bone under dry and physiological drilling conditions

NASA Astrophysics Data System (ADS)

Xu, Linlin; Wang, Chengyong; Jiang, Min; He, Huiyu; Song, Yuexian; Chen, Hanyuan; Shen, Jingnan; Zhang, Jiayong

2014-11-01

Many researches on drilling force and temperature have been done with the aim to reduce the labour intensiveness of surgery, avoid unnecessary damage and improve drilling quality. However, there has not been a systematic study of mid- and high-speed drilling under dry and physiological conditions(injection of saline). Furthermore, there is no consensus on optimal drilling parameters. To study these parameters under dry and physiological drilling conditions, pig humerus bones are drilled with medical twist drills operated using a wide range of drilling speeds and feed rates. Drilling force and temperature are measured using a YDZ-II01W dynamometer and a NEC TVS-500EX thermal infrared imager, respectively, to evaluate internal bone damage. To evaluate drilling quality, bone debris and hole morphology are observed by SEM(scanning electron microscopy). Changes in drilling force and temperature give similar results during drilling such that the value of each parameter peaks just before the drill penetrates through the osteon of the compact bone into the trabeculae of the spongy bone. Drilling temperatures under physiological conditions are much lower than those observed under dry conditions, while a larger drilling force occurs under physiological conditions than dry conditions. Drilling speed and feed rate have a significant influence on drilling force, temperature, bone debris and hole morphology. The investigation of the effect of drilling force and temperature on internal bone damage reveals that a drilling speed of 4500 r/min and a feed rate of 50 mm/min are recommended for bone drilling under physiological conditions. Drilling quality peaks under these optimal parameter conditions. This paper proposes the optimal drilling parameters under mid- and high-speed surgical drilling, considering internal bone damage and drilling quality, which can be looked as a reference for surgeons performing orthopedic operations.

Effect of recombinant human bone morphogenetic protein-2 on bone regeneration and osseointegration of dental implants.

PubMed

Sykaras, N; Triplett, R G; Nunn, M E; Iacopino, A M; Opperman, L A

2001-08-01

Recombinant human bone morphogenetic protein-2 (rhBMP-2) induced bone regeneration and osseointegration was evaluated in bony defects created within the hollow chamber of endosseous dental implants in 14 foxhound dogs. Bilateral extractions of mandibular premolars were performed and surgical implantation of 104 hollow cylinder implants followed after 8 weeks of healing. Experimental implants had their hollow chamber filled with 20 microg of rhBMP-2 delivered with a bovine collagen carrier, whereas the control implants had their apical chamber left empty. Dogs were followed for 2, 4, 8 and 12 weeks. Histomorphometric evaluation and immunohistochemical analysis were performed. Minimal bone was regenerated at 2 weeks for both groups. At 4 weeks, bone fill averaged 23.48% for the rhBMP-2 and 5.98% for the control group (P<0.05). At 8 weeks, mean bone fill was 20.94% and 7.75% for the rhBMP-2 and the controls, respectively (P<0.05). At 12 weeks, mean bone fill was 31.39% and 24.31% for the rhBMP-2 and control implants, respectively (P>0.05). Bone-implant contact (BIC) increased for both groups over time and at 8 weeks the rhBMP-2 BIC value was 18.65% and for the control 7.22% (P<0.05). At 12 weeks, the BIC was 43.78% and 21.05% for the rhBMP-2 and the control group, respectively (P<0.05). Immunohistochemical staining for type II collagen was positive only for parts of the collagen carrier and formation of cartilaginous intermediate was not observed in any of the specimens. The results suggest that, in confined defects adjacent to dental implants, rhBMP-2 can induce bone regeneration in close apposition to the implant surface.

Influence of different modifications of a calcium phosphate bone cement on adhesion, proliferation, and osteogenic differentiation of human bone marrow stromal cells.

PubMed

Vater, Corina; Lode, Anja; Bernhardt, Anne; Reinstorf, Antje; Heinemann, Christiane; Gelinsky, Michael

2010-03-15

Collagen and noncollagenous proteins of the extracellular bone matrix are able to stimulate bone cell activities and bone healing. The modification of calcium phosphate bone cements used as temporary bone replacement materials with these proteins seems to be a promising approach to accelerate new bone formation. In this study, we investigated adhesion, proliferation, and osteogenic differentiation of human bone marrow stromal cells (hBMSC) on Biocement D/collagen composites which have been modified with osteocalcin and O-phospho-L-serine. Modification with osteocalcin was carried out by its addition to the cement precursor before setting as well as by functionalization of the cement samples after setting and sterilization. hBMSC were cultured on these samples for 28 days with and without osteogenic supplements. We found a positive impact especially of the phosphoserine-modifications but also of both osteocalcin-modifications on differentiation of hBMSC indicated by higher expression of the osteoblastic markers matrix metalloproteinase-13 and bone sialo protein II. For hBMSC cultured on phosphoserine-containing composites, an increased proliferation has been observed. However, in case of the osteocalcin-modified samples, only osteocalcin adsorbed after setting and sterilization of the cement samples was able to promote initial adhesion and proliferation of hBMSC. The addition of osteocalcin before setting results in a finer microstructure but the biological activity of osteocalcin might be impaired due to the sterilization process. Thus, our data indicate that the initial adhesion and proliferation of hBMSC is enhanced rather by the biological activity of osteocalcin than by the finer microstructure. (c) 2009 Wiley Periodicals, Inc.

Micro-finite-element method to assess elastic properties of trabecular bone at micro- and macroscopic level.

PubMed

Rieger, R; Auregan, J C; Hoc, T

2018-03-01

The objective of the present study is to assess the mechanical behavior of trabecular bone based on microCT imaging and micro-finite-element analysis. In this way two methods are detailed: (i) direct determination of macroscopic elastic property of trabecular bone; (ii) inverse approach to assess mechanical properties of trabecular bone tissue. Thirty-five females and seven males (forty-two subjects) mean aged (±SD) 80±11.7 years from hospitals of Assistance publique-Hôpitaux de Paris (AP-HP) diagnosed with osteoporosis following a femoral neck fracture due to a fall from standing were included in this study. Fractured heads were collected during hip replacement surgery. Standardized bone cores were removed from the femoral head's equator by a trephine in a water bath. MicroCT images acquisition and analysis were performed with CTan ® software and bone volume fraction was then determined. Micro-finite-element simulations were per-formed using Abaqus 6.9-2 ® software in order to determine the macroscopic mechanical behaviour of the trabecular bone. After microCT acquisition, a longitudinal compression test was performed and the experimental macroscopic Young's Modulus was extracted. An inverse approach based on the whole trabecular bone's mechanical response and micro-finite-element analysis was performed to determine microscopic mechanical properties of trabecular bone. In the present study, elasticity of the tissue was shown to be similar to that of healthy tissue but with a lower yield stress. Classical histomorphometric analysis form microCT imaging associated with an inverse micro-finite-element method allowed to assess microscopic mechanical trabecular bone parameters. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Role of sclerostin in bone and cartilage and its potential as a therapeutic target in bone diseases

PubMed Central

2014-01-01

Sclerostin is a small protein expressed by the SOST gene in osteocytes, bone cells that respond to mechanical stress applied to the skeleton and appear to play an important role in the regulation of bone remodeling. When sclerostin binds to its receptors on the cell surface of osteoblasts, a downstream cascade of intracellular signaling is initiated, with the ultimate effect of inhibiting osteoblastic bone formation. Recent studies have shown that the SOST gene is also expressed by articular chondrocytes and that modulation of its activity may have effects on articular cartilage and subchondral bone. The role of sclerostin in the pathogenesis of osteoarthritis in humans has not yet been defined, and the potential utility of treating osteoarthritis with interventions that alter sclerostin is not known. Rare genetic skeletal disorders in humans with low sclerostin levels, such as sclerosteosis and van Buchem disease, have been associated with a high bone mineral density (BMD) phenotype and low risk of fractures. This has led to the concept that antisclerostin interventions might be useful in the treatment of patients with osteoporosis and skeletal disorders associated with low bone mass. Compounds that inhibit sclerostin have been shown to stimulate bone formation and reduce bone resorption, with a robust increase in BMD. Investigational monoclonal antibodies to sclerostin, including romosozumab, blosozumab, and BPS804, have advanced to phase II clinical trials or beyond. If antisclerostin therapy is found to have beneficial effects on clinical endpoints, such as reduction of fracture risk or improvement in quality of life in patients with osteoarthritis, with a favorable balance of benefit and risk, then this class of compounds may become a prominent addition to the options for therapy of osteoporosis and other skeletal disorders. PMID:24688605

Comparative evaluation of different calcium phosphate-based bone graft granules - an in vitro study with osteoblast-like cells.

PubMed

Bernhardt, Anne; Lode, Anja; Peters, Fabian; Gelinsky, Michael

2013-04-01

Granule-shaped calcium phosphate-based bone graft materials are often required for bone regeneration especially in implant dentistry. Two newly developed bone graft materials are Ceracell(®) , an open-celled highly porous bioceramic from β-tricalcium phosphate (β-TCP) under addition of bioglass and Osseolive(®) , an open porous glass ceramic with the general formula Ca2 KNa(PO4 )2 . The goal of this study was to characterize different modifications of the two bone graft materials in vitro in comparison to already established ceramic bone grafts Cerasorb M(®) , NanoBone(®) and BONIT Matrix(®) . Adhesion and proliferation of SaOS-2 osteoblast-like cells were evaluated quantitatively by determining DNA content and lactate dehydrogenase (LDH) activity and qualitatively by scanning electron microscopy (SEM). In addition, MTT cell-vitality staining was applied to confirm the attachment of viable cells to the different materials. Osteogenic differentiation was evaluated by measurement of alkaline phosphatase (ALP) activity as well as gene expression analysis of osteogenic markers using reverse transcriptase PCR. DNA content and LDH activity revealed good cell attachment and proliferation for Ceracell and Cerasorb M. When pre-incubated with cell-culture medium, also Osseolive showed good cell attachment and proliferation. Attachment and proliferation of osteoblast-like cells on NanoBone and BONIT Matrix was very low, even after pre-incubation with cell-culture medium. Specific ALP activity on Ceracell(®) , Osseolive (®) and Cerasorb M(®) increased with time and expression of bone-related genes ALP, osteonectin, osteopontin and bone sialoprotein II was demonstrated. Ceracell as well as Osseolive granules support proliferation and osteogenic differentiation in vitro and may be promising candidates for in vivo applications. © 2011 John Wiley & Sons A/S.

Temperature and time variations during osteotomies performed with different piezosurgical devices: an in vitro study.

PubMed

Delgado-Ruiz, R A; Sacks, D; Palermo, A; Calvo-Guirado, J L; Perez-Albacete, C; Romanos, G E

2016-09-01

The aim of this experimental in vitro study was to evaluate the effects of the piezoelectric device in temperature and time variations in standardized osteotomies performed with similar tip inserts in bovine bone blocks. Two different piezosurgical devices were used the OE-F15(®) (Osada Inc., Los Angeles, California, USA) and the Surgybone(®) (Silfradent Inc., Sofia, Forli Cesena, Italy). Serrated inserts with similar geometry were coupled with each device (ST94 insert/test A and P0700 insert/test B). Osteotomies 10 mm long and 3 mm deep were performed in bone blocks resembling type II (dense) and type IV (soft) bone densities with and without irrigation. Thermal changes and time variations were recorded. The effects of bone density, irrigation, and device on temperature changes and time necessary to accomplish the osteotomies were analyzed. Thermal analysis showed significant higher temperatures during piezosurgery osteotomies in hard bone without irrigation (P < 0.05). The type of piezosurgical device did not influence thermal variations (P > 0.05). Time analysis showed that the mean time values necessary to perform osteotomies were shorter in soft bone than in dense bone (P < 0.05). Within the limitations of this in vitro study, it may be concluded that the temperature increases more in piezosurgery osteotomies in dense bone without irrigation; the time to perform the osteotomy with piezosurgery is shorter in soft bone compared to hard bone; and the piezosurgical device have a minimal influence in the temperature and time variations when a similar tip design is used during piezosurgery osteotomies. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A roaring trade? The legal trade in Panthera leo bones from Africa to East-Southeast Asia.

PubMed

Williams, Vivienne L; Loveridge, Andrew J; Newton, David J; Macdonald, David W

2017-01-01

The African lion is the only big cat listed on CITES Appendix II, and the only one for which international commercial trade is legal under CITES. The trade in lion body parts, and especially the contentious trade in bones from South Africa to Asia, has raised concerns spanning continents and cultures. Debates were amplified at the 2016 CITES Conference of the Parties (CoP17) when a proposal to up-list lions to Appendix I was not supported and a compromise to keep them on Appendix II, with a bone trade quota for South Africa, was reached instead. CoP17 underscored a need for further information on the lion bone trade and the consequences for lions across the continent. Legal international trade in bones to Asia, allegedly to supply the substitute 'tiger bone' market, began in South Africa in February 2008 when the first CITES permits were issued. It was initially unclear the degree to which bones were sourced from captive-origin lions, and whether trade was a threat to wild lion populations. Our original assessment of the legal CITES-permitted lion bone trade from South Africa to East-Southeast Asia was for the period 2008-2011 (published 2015). In this paper, we consolidate new information that has become available for 2012-2016, including CITES reports from other African countries, and data on actual exports for three years to 2016 supplied by a freight forwarding company. Thus, we update the figures on the legal trade in lion bones from Africa to East-Southeast Asia in the period 2008-2016. We also contextualise the basis for global concerns by reviewing the history of the trade and its relation to tigers, poaching and wildlife trafficking. CITES permits issued to export bones escalated from ±314y-1 skeletons from 2008-2011, to ±1312y-1 skeletons from 2013-2015. South Africa was the only legal exporter of bones to Asia until 2013 when Namibia issued permits to export skeletons to Vietnam. While CITES permits to export ±5363 skeletons from Africa to Asia from 2008-2015 were issued (99.1% from South Africa; 0.7% from Namibia) (51% for Laos), actual exports were less than stated on the permits. However, information on actual exports from 2014-2016 indicated that >3400 skeletons were exported in that period. In total, >6000 skeletons weighing no less than 70 tonnes have been shipped to East-Southeast Asia since 2008. Since few wild lions are hunted and poached within South African protected areas, skeletons for the legal trade appear to be derived from captive bred lions. However, confirmation of a 116kg shipment from Uganda to Laos, and reports of lion poaching in neighbouring countries, indicate that urgent proactive monitoring and evaluation of the legal and illegal trade is necessary in African lion range states where vulnerable wild lion populations are likely to be adversely affected.

Importance of increased intraosseous pressure in the development of osteonecrosis of the femoral head: implications for treatment

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

Hungerford, D.S.; Lennox, D.W.

1985-10-01

Early diagnosis of osteonecrosis by radiograph, bone scan, CT scan, magnetic resonance imaging (MRI), intraosseous pressure measurement, or intraosseous venogram can lead to early successful treatment. For early (Ficat stages I and II) osteonecrosis of the hip, core decompression can provide diagnostic confirmation and pain relief and may prevent progression of disease. For more advanced disease (Ficat stages II and IV), osteotomy, endoprosthetic or bipolar prosthetic replacement, total hip arthroplasty, and arthrodesis are surgical options.86 references.

Histone deacetylases (HDAC) in physiological and pathological bone remodelling.

PubMed

Cantley, M D; Zannettino, A C W; Bartold, P M; Fairlie, D P; Haynes, D R

2017-02-01

Histone deacetylases (HDACs) 2 play important roles in the epigenetic regulation of gene expression in cells and are emerging therapeutic targets for treating a wide range of diseases. HDAC inhibitors (HDACi) 3 that act on multiple HDAC enzymes have been used clinically to treat a number of solid and hematological malignancies. HDACi are also currently being studied for their efficacy in non-malignant diseases, including pathologic bone loss, but this has necessitated a better understanding of the roles of individual HDAC enzymes, particularly the eleven zinc-containing isozymes. Selective isozyme-specific inhibitors currently being developed against class I HDACs (1, 2, 3 and 8) and class II HDACs (4, 5, 6, 7, 9 and 10) will be valuable tools for elucidating the roles played by individual HDACs in different physiological and pathological settings. Isozyme-specific HDACi promise to have greater efficacy and reduced side effects, as required for treating chronic disease over extended periods of time. This article reviews the current understanding of roles for individual HDAC isozymes and effects of HDACi on bone cells, (osteoblasts, osteoclasts and osteocytes), in relation to bone remodelling in conditions characterised by pathological bone loss, including periodontitis, rheumatoid arthritis and myeloma bone disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor

PubMed Central

1992-01-01

Antigen-presenting, major histocompatibility complex (MHC) class II- rich dendritic cells are known to arise from bone marrow. However, marrow lacks mature dendritic cells, and substantial numbers of proliferating less-mature cells have yet to be identified. The methodology for inducing dendritic cell growth that was recently described for mouse blood now has been modified to MHC class II- negative precursors in marrow. A key step is to remove the majority of nonadherent, newly formed granulocytes by gentle washes during the first 2-4 d of culture. This leaves behind proliferating clusters that are loosely attached to a more firmly adherent "stroma." At days 4-6 the clusters can be dislodged, isolated by 1-g sedimentation, and upon reculture, large numbers of dendritic cells are released. The latter are readily identified on the basis of their distinct cell shape, ultrastructure, and repertoire of antigens, as detected with a panel of monoclonal antibodies. The dendritic cells express high levels of MHC class II products and act as powerful accessory cells for initiating the mixed leukocyte reaction. Neither the clusters nor mature dendritic cells are generated if macrophage colony-stimulating factor rather than granulocyte/macrophage colony-stimulating factor (GM-CSF) is applied. Therefore, GM-CSF generates all three lineages of myeloid cells (granulocytes, macrophages, and dendritic cells). Since > 5 x 10(6) dendritic cells develop in 1 wk from precursors within the large hind limb bones of a single animal, marrow progenitors can act as a major source of dendritic cells. This feature should prove useful for future molecular and clinical studies of this otherwise trace cell type. PMID:1460426

A 5-year comparison of marginal bone level following immediate loading of single-tooth implants placed in healed alveolar ridges and extraction sockets in the maxilla

PubMed Central

Berberi, Antoine N.; Sabbagh, Joseph M.; Aboushelib, Moustafa N.; Noujeim, Ziad F.; Salameh, Ziad A.

2014-01-01

Purpose: The aim of present investigation was to evaluate marginal bone level after 5-year follow-up of implants placed in healed ridges and fresh extraction sockets in maxilla with immediate loading protocol. Materials and Methods: Thirty-six patients in need of a single-tooth replacement in the anterior maxilla received 42 Astra Tech implants (Astra Tech Implant system™, Dentsply Implants, Mölndal, Sweden). Implants were placed either in healed ridges (group I) or immediately into fresh extraction sockets (group II). Implants were restored and placed into functional loading immediately by using a prefabricated abutment. Marginal bone level relative to the implant reference point was recorded at implant placement, crown cementation, 12, 36, and 60 months following loading using intra-oral radiographs. Measurements were made on the mesial and distal sides of each implant. Results: Overall, two implants were lost from the group II, before final crown cementation: they were excluded from the study. The mean change in marginal bone loss (MBL) after implant placement was 0.26 ± 0.161 mm for 1 year, and 0.26 ± 0.171 mm for 3 years, and 0.21 ± 0.185 mm for 5 years in extraction sockets and was 0.26 ± 0.176 mm for 1 year and 0.21 ± 0.175 mm for 3 years, and 0.19 ± 0.172 mm for 5 years in healed ridges group. Significant reduction of marginal bone was more pronounced in implants inserted in healed ridges (P < 0.041) compared to fresh surgical extraction sockets (P < 0.540). Significant MBL was observed on the mesial side of the implant after cementation of the provisional (P < 0.007) and after 12 months (P < 0.034) compared to the distal side which remained stable for 3 and 5 years observation period. Conclusions: Within the limitations of this study, responses of local bone to immediately loaded implants placed either in extraction sockets or healed ridges were similar. Functional loading technique by using prefabricated abutment placed during the surgery time seems to maintain marginal bone around implant in both healed and fresh extraction sites. PMID:24550840

Ultrastructure Organization of Human Trabeculae Assessed by 3D sSAXS and Relation to Bone Microarchitecture

PubMed Central

Guizar-Sicairos, Manuel; Gschwend, Oliver; Hangartner, Peter; Bunk, Oliver; Müller, Ralph; Schneider, Philipp

2016-01-01

Although the organization of bone ultrastructure, i.e. the orientation and arrangement of the mineralized collagen fibrils, has been in the focus of research for many years for cortical bone, and many models on the osteonal arrangement have been proposed, limited attention has been paid to trabecular bone ultrastructure. This is surprising because trabeculae play a crucial role for the mechanical strength of several bone sites, including the vertebrae and the femoral head. On this account, we first validated a recently developed method (3D sSAXS or 3D scanning small-angle X-ray scattering) for investigating bone ultrastructure in a quantitative and spatially resolved way, using conventional linearly polarized light microscopy as a gold standard. While both methods are used to analyze thin tissue sections, in contrast to polarized light microscopy, 3D sSAXS has the important advantage that it provides 3D information on the orientation and arrangement of bone ultrastructure. In this first study of its kind, we used 3D sSAXS to investigate the ultrastructural organization of 22 vertebral trabeculae of different alignment, types and sizes, obtained from 4 subjects of different ages. Maps of ultrastructure orientation and arrangement of the trabeculae were retrieved by stacking information from consecutive 20-μm-thick bone sections. The organization of the ultrastructure was analyzed in relation to trabecular microarchitecture obtained from computed tomography and to relevant parameters such as distance to trabecular surface, local curvature or local bone mineralization. We found that (i) ultrastructure organization is similar for all investigated trabeculae independent of their particular characteristics, (ii) bone ultrastructure exhibiting a high degree of orientation was arranged in domains, (iii) highly oriented ultrastructural areas were located closer to the bone surface, (iv) the ultrastructure of the human trabecular bone specimens followed the microarchitecture, being oriented mostly parallel to bone surface, and (v) local surface curvature seems to have an effect on the ultrastructure organization. Further studies that investigate bone ultrastructure orientation and arrangement are needed in order to understand its organization and consequently its relation to bone biology and mechanics. PMID:27547973

Bone augmentation at peri-implant dehiscence defects comparing a synthetic polyethylene glycol hydrogel matrix vs. standard guided bone regeneration techniques.

PubMed

Thoma, Daniel S; Jung, Ui-Won; Park, Jin-Young; Bienz, Stefan P; Hüsler, Jürg; Jung, Ronald E

2017-07-01

The aim of the study was to test whether or not the use of a polyethylene glycol (PEG) hydrogel with or without the addition of an arginylglycylaspartic acid (RGD) sequence applied as a matrix in combination with hydroxyapatite/tricalciumphosphate (HA/TCP) results in similar peri-implant bone regeneration as traditional guided bone regeneration procedures. In 12 beagle dogs, implant placement and peri-implant bone regeneration were performed 2 months after tooth extraction in the maxilla. Two standardized box-shaped defects were bilaterally created, and dental implants were placed in the center of the defects with a dehiscence of 4 mm. Four treatment modalities were randomly applied: i)HA/TCP mixed with a synthetic PEG hydrogel, ii)HA/TCP mixed with a synthetic PEG hydrogel supplemented with an RGD sequence, iii)HA/TCP covered with a native collagen membrane (CM), iv)and no bone augmentation (empty). After a healing period of 8 or 16 weeks, micro-CT and histological analyses were performed. Histomorphometric analysis revealed a greater relative augmented area for groups with bone augmentation (43.3%-53.9% at 8 weeks, 31.2%-42.8% at 16 weeks) compared to empty controls (22.9% at 8 weeks, 1.1% at 16 weeks). The median amount of newly formed bone was greatest in group CM at both time-points. Regarding the first bone-to-implant contact, CM was statistically significantly superior to all other groups at 8 weeks. Bone can partially be regenerated at peri-implant buccal dehiscence defects using traditional guided bone regeneration techniques. The use of a PEG hydrogel applied as a matrix mixed with a synthetic bone substitute material might lack a sufficient stability over time for this kind of defect. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Study of migration and distribution of bone marrow cells transplanted animals with B16 melanoma ].

PubMed

Poveshchenko, A F; Solovieva, A O; Zubareva, K E; Strunkin, D N; Gricyk, O B; Poveshchenko, O V; Shurlygina, A V; Konenkov, V I

2017-01-01

Purpose. Reveal features migration and distribution of syngeneic bone marrow cells (BMC) and subpopulations (MSC) after transplantation into the recipient carrier B16 melanoma bodies. Methods. We used mouse male and female C57BL/6 mice. Induction of Tumor Growth: B16 melanoma cells implanted subcutaneously into right hind paw of female C57BL/6 mice at a dose of 2.5 x 105 cells / mouse. migration study in vivo distribution and BMC and MSC was performed using genetic markers - Y-chromosome specific sequence line male C57Bl/6 syngeneic intravenous transplantation in females using the polymerase chain reaction (PCR) in real time on Authorized Termal Cycler - Light Cycler 480 II / 96 (Roche). Introduction suspension of unseparated bone marrow cells, mesenchymal stem cells from donor to recipient male mice (syngeneic recipient female C57BL/6), followed by isolation of recipients of organs was performed at regular intervals, then of organ recipients isolated DNA. Results. It was shown that bone marrow cells positive for Y-chromosome in migrate lymphoid (lymph nodes, spleen, bone marrow) or in non-lymphoid organs (liver, heart, brain, skin) syngeneic recipients. In addition to the migration of cells from the bone marrow to other organs, there is a way back migration of cells from the circulation to the bone marrow. B16 melanoma stimulates the migration of transplanted MSCs and BMC in bone marrow. It is found that tumor growth enhanced migration of transplanted bone marrow cells, including populations of MSCs in the bone marrow. In the early stages of tumor formation MSC migration activity higher than the BMC. In the later stages of tumor formation undivided population of bone marrow cells migrate to the intense swelling compared with a population of MSCs. Conclusion. The possibility of using bone marrow MSCs for targeted therapy of tumor diseases, because migration of MSCs in tumor tissue can be used to effectively deliver anticancer drugs.

Low bone mineral density in ambulatory persons with cerebral palsy? A systematic review.

PubMed

Mus-Peters, Cindy T R; Huisstede, Bionka M A; Noten, Suzie; Hitters, Minou W M G C; van der Slot, Wilma M A; van den Berg-Emons, Rita J G

2018-05-22

Non-ambulatory persons with cerebral palsy are prone to low bone mineral density. In ambulatory persons with cerebral palsy, bone mineral density deficits are expected to be small or absent, but a consensus conclusion is lacking. In this systematic review bone mineral density in ambulatory persons with cerebral palsy (Gross Motor Function Classification Scales I-III) was studied. Medline, Embase, and Web of Science were searched. According to international guidelines, low bone mineral density was defined as Z-score ≤ -2.0. In addition, we focused on Z-score ≤ -1.0 because this may indicate a tendency towards low bone mineral density. We included 16 studies, comprising 465 patients aged 1-65 years. Moderate and conflicting evidence for low bone mineral density (Z-score ≤ -2.0) was found for several body parts (total proximal femur, total body, distal femur, lumbar spine) in children with Gross Motor Function Classification Scales II and III. We found no evidence for low bone mineral density in children with Gross Motor Function Classification Scale I or adults, although there was a tendency towards low bone mineral density (Z-score ≤ -1.0) for several body parts. Although more high-quality research is needed, results indicate that deficits in bone mineral density are not restricted to non-ambulatory people with cerebral palsy. Implications for Rehabilitation Although more high-quality research is needed, including adults and fracture risk assessment, the current study indicates that deficits in bone mineral density are not restricted to non-ambulatory people with CP. Health care professionals should be aware that optimal nutrition, supplements on indication, and an active lifestyle, preferably with weight-bearing activities, are important in ambulatory people with CP, also from a bone quality point-of-view. If indicated, medication and fall prevention training should be prescribed.

CD4 T Cells and Major Histocompatibility Complex Class II Expression Influence Worm Expulsion and Increased Intestinal Muscle Contraction during Trichinella spiralis Infection

PubMed Central

Vallance, Bruce A.; Galeazzi, Francesca; Collins, Stephen M.; Snider, Denis P.

1999-01-01

Expulsion of intestinal nematode parasites and the associated increased contraction by intestinal muscle are T cell dependent, since both are attenuated in athymic rodents. The CD4 T-cell subset has been strongly associated with worm expulsion; however, the relationship between these cells, antigen presentation, and worm expulsion is not definitive and the role of these factors in intestinal muscle hypercontractility has not been defined. We infected C57BL/6, athymic, CD4-deficient, CD8α-deficient, and major histocompatibility complex class II (MHC II)-deficient (C2d) mice with Trichinella spiralis larvae. We examined intestinal worm numbers, longitudinal muscle contraction, and MHC II expression. Numerous MHC II-positive cells were identified within the muscularis externa of infected but not uninfected C57BL/6 mice. C57BL/6 and CD8α-deficient mice developed large increases in muscle contraction, expelling the parasite by day 21. Athymic and C2d mice exhibited much smaller increases in muscle contraction and delayed parasite expulsion. CD4-deficient mice exhibited intermediate levels of muscle contraction and delayed parasite expulsion. To further examine the role of MHC II and CD4 T cells, we irradiated C2d mice and reconstituted them with C57BL/6 bone marrow alone or with C57BL/6 CD4 T cells. C57BL/6 bone marrow alone did not affect muscle function or worm expulsion in recipient C2d mice. Partial CD4 T-cell reconstitution was sufficient to restore increased muscle contraction but not worm expulsion. Thus, hematopoietic MHC II expression alone is insufficient for the development of muscle hypercontractility and worm expulsion, but the addition of even small numbers of CD4 T cells was sufficient to induce intestinal muscle pathophysiology. PMID:10531271

Relationships of muscle strength and bone mineral density in ambulatory children with cerebral palsy.

PubMed

Chen, C-L; Lin, K-C; Wu, C-Y; Ke, J-Y; Wang, C-J; Chen, C-Y

2012-02-01

This work explores the relationships of muscle strength and areal bone mineral density (aBMD) in ambulatory children with cerebral palsy (CP). The knee extensor strength, but not motor function, was related to aBMD. Thus, muscle strength, especially antigravity muscle strength, was more associated with aBMD in these children than motor function. Muscle strength is related to bone density in normal children. However, no studies have examined these relationships in ambulatory children with CP. This work explores the relationships of muscle strength and aBMD in ambulatory children with CP. Forty-eight ambulatory children with spastic CP, aged 5-15 years, were classified into two groups based on Gross Motor Function Classification System levels: I (n = 28) and II (n = 20). Another 31 normal development (ND) children were recruited as the comparison group for the aBMD. Children with CP underwent assessments of growth, lumbar and distal femur aBMD, Gross Motor Function Measure-66 (GMFM-66), and muscle strength of knee extensor and flexor by isokinetic dynamometer. The distal femur aBMD, but not lumbar aBMD, was lower in children with CP than in ND children (p < 0.05). Children with level I had greater knee flexor strength and GMFM-66 scores than those with level II (p < 0.001). However, the knee extensor strength and distal femur and lumbar aBMD did not differ between two groups. Regression analysis revealed the weight and knee extensor strength, but not GMFM-66 scores, were related positively to the distal femur and lumbar aBMD (adjusted r (2) = 0.56-0.65, p < 0.001). These results suggest the muscle strength, especially antigravity muscle strength, were more associated with the bone density of ambulatory children with CP than motor function. The data may allow clinicians for early identifying the ambulatory CP children of potential low bone density.

Perlecan-containing pericellular matrix regulates solute transport and mechanosensing within the osteocyte lacunar-canalicular system

PubMed Central

Wang, Bin; Lai, Xiaohan; Price, Christopher; Thompson, William R.; Li, Wen; Quabili, Tonima R.; Tseng, Wei-Ju; Liu, Xiaowei Sherry; Zhang, Hong; Pan, Jun; Kirn-Safran, Catherine B.; Farach-Carson, Mary C.; Wang, Liyun

2013-01-01

The pericellular matrix (PCM), a thin “coating” surrounding nearly all mammalian cells, plays a critical role in many cell-surface phenomena. In osteocytes, the PCM is believed to control both “outside-in” (mechanosensing) and “inside-out” (signaling molecule transport) processes. However, the osteocytic PCM is challenging to study in situ because it is thin (~100nm) and enclosed in mineralized matrix. To this end, we recently developed a novel tracer velocimetry approach that combined fluorescence recovery after photobleaching (FRAP) imaging with hydrodynamic modeling to quantify the osteocytic PCM in young murine bone (Wang et al., J Bone Miner Res. 2013; 28:1075–86). In this study, we applied the technique to older mice expressing or deficient for perlecan/HSPG2, a large heparan-sulfate proteoglycan normally secreted in osteocytic PCM. The objectives were to i) characterize transport within an altered PCM; ii) to test the sensitivity of our approach in detecting the PCM alterations; and iii) to dissect the roles of the PCM in osteocyte mechanosensing. We found that i) solute transport increases in the perlecan-deficient (hypomorphic: Hypo) mice compared with control mice; ii) PCM fiber density decreases with aging and perlecan deficiency; iii) the osteocytes in the Hypo bones are predicted to experience higher shear stress (+34%), but decreased fluid drag force (−35%) under 3N peak tibial loading, and iv) when subjected to tibial loading in a preliminary in vivo experiment, the Hypo mice did not respond to the anabolic stimuli as CTL mice. These findings support the hypothesis that the PCM fibers act as osteocyte’s sensing antennae, regulating load-induced cellular stimulations and thus bone’s sensitivity and in vivo bone adaptation. If this hypothesis is further confirmed, osteocytic PCM could be new targets to develop osteoporosis treatments by modulating bone’s intrinsic sensitivity to mechanical loading and be used to design patient-specific exercise regimens to promote bone formation. PMID:24115222

The ACE-2/Ang1-7/Mas cascade enhances bone structure and metabolism following angiotensin-II type 1 receptor blockade.

PubMed

Abuohashish, Hatem M; Ahmed, Mohammed M; Sabry, Dina; Khattab, Mahmoud M; Al-Rejaie, Salim S

2017-07-15

The renin angiotensin system (RAS) regulates numerous systemic functions and is expressed locally in skeletal tissues. Angiotensin1-7 (Ang1-7) is a beneficial member of the RAS, and the therapeutic effects of a large number of angiotensin receptors blockers (ARBs) are mediated by an Ang1-7-dependent cascade. This study examines whether the reported osteo-preservative effects of losartan are mediated through the angiotensin converting enzyme2 (ACE-2)/Ang1-7/Mas pathway in ovariectomized (OVX) rats. Sham and OVX animals received losartan (10mg/kg/d p.o.) for 6 weeks. A specific Mas receptor blocker (A-779) was delivered via mini-osmotic pumps during the losartan treatment period. Serum and urine bone metabolism biomarker levels were measured. Bone trabecular and cortical morphometry were quantified in distal femurs, whereas mineral contents were estimated in ashed bones, serum and urine. Finally, the expression of RAS components, the receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) was determined. Losartan significantly improved the elevated bone metabolism marker levels and altered trabecular and cortical structures in OVX animals, and restored normal urinary and skeletal mineral levels. Mas receptor inhibition significantly abolished all osteo-protective effects of losartan and enhanced the deleterious effects of OVX. Losartan enhanced OVX-induced up-regulation of ACE-1, AngII, angiotensin type 1 (AT 1 ) receptor and RANKL expression, and increased ACE-2, Ang1-7, Mas and OPG expression in OVX animals. However, A-779 significantly eradicated the effects of losartan on RAS components and RANKL/OPG expression. Thus, Ang1-7 are involved in the osteo-preservative effects of losartan via Mas receptor, which may add therapeutic value to this well-known antihypertensive agent. Copyright © 2017 Elsevier B.V. All rights reserved.

Lead in bone II: skeletal-lead content as an indicator of lifetime lead ingestion and the social correlates in an archaeological population

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

Aufderheide, A.C.; Neiman, F.D.; Wittmers, L.E. Jr.

1981-07-01

Measurements of skeletal-lead content (by atomic absorption spectroscopy) were made for 16 individuals recovered from a Colonial (1670-1730) plantation cemetery in Virginia. Archaeological and historical evidence allowed the identification of two social groups (plantation proprietors and laborers) within this small population, each with vastly different estimated lifetime lead exposure, reflecting different living conditions. Measured bone-lead levels confirmed these differences. The character of plantation social organization proved a more important determinant of skeletal-lead content in the individuals studied than age, sex or race.

Open Label, Phase II Study to Evaluate Efficacy and Safety of Oral Nilotinib in Philadelphia Positive (Ph+) Chronic Myelogenous Leukemia (CML) Pediatric Patients.

ClinicalTrials.gov

2018-04-20

Leukemia; Leukemia,Pediatric; Leukemia, Myleiod; Leukemia, Mylegenous, Chronic; Leukemia, Mylegenous, Accelerated; BCR-ABL Positive; Myeloproliferative Disorder; Bone Marrow Disease; Hematologic Diseases; Neoplastic Processes; Imatinib; Dasatinib; Enzyme Inhibitor; Protein Kinase Inhibitor

Prdm5 Regulates Collagen Gene Transcription by Association with RNA Polymerase II in Developing Bone

PubMed Central

Galli, Giorgio Giacomo; Honnens de Lichtenberg, Kristian; Carrara, Matteo; Hans, Wolfgang; Wuelling, Manuela; Mentz, Bettina; Multhaupt, Hinke Arnolda; Fog, Cathrine Kolster; Jensen, Klaus Thorleif; Rappsilber, Juri; Vortkamp, Andrea; Coulton, Les; Fuchs, Helmut; Gailus-Durner, Valérie; Hrabě de Angelis, Martin; Calogero, Raffaele Adolfo; Couchman, John Robert; Lund, Anders Henrik

2012-01-01

PRDM family members are transcriptional regulators involved in tissue specific differentiation. PRDM5 has been reported to predominantly repress transcription, but a characterization of its molecular functions in a relevant biological context is lacking. We demonstrate here that Prdm5 is highly expressed in developing bones; and, by genome-wide mapping of Prdm5 occupancy in pre-osteoblastic cells, we uncover a novel and unique role for Prdm5 in targeting all mouse collagen genes as well as several SLRP proteoglycan genes. In particular, we show that Prdm5 controls both Collagen I transcription and fibrillogenesis by binding inside the Col1a1 gene body and maintaining RNA polymerase II occupancy. In vivo, Prdm5 loss results in delayed ossification involving a pronounced impairment in the assembly of fibrillar collagens. Collectively, our results define a novel role for Prdm5 in sustaining the transcriptional program necessary to the proper assembly of osteoblastic extracellular matrix. PMID:22589746

Immunohistochemical localization of bone morphogenetic proteins and the receptors in epiphyseal growth plate.

PubMed

Yazaki, Y; Matsunaga, S; Onishi, T; Nagamine, T; Origuchi, N; Yamamoto, T; Ishidou, Y; Imamura, T; Sakou, T

1998-01-01

The expression of bone morphogenetic proteins (BMPs) and BMP receptors (BMPRs) in the epiphyseal growth plate has not been clarified. In this study, we studied immunohistochemically the spatial and temporal localization of BMP-2/4, osteogenic protein-1 (OP-1, or BMP-7), and BMP receptors (BMPR-IA, BMPR-IB, and BMPR-II) in the epiphyseal plate of growing rats. The proximal parts of tibia in growing rats were observed. At 12 weeks after birth, BMP-2/4 and OP-1 were expressed markedly in proliferating and maturing chondrocytes. BMPR-IA, IB and II were clearly co-expressed in proliferating and maturing chondrocytes, and the expression was decreased in hypertrophic chondrocytes. At 24 weeks, the expression of BMP-2/4 and OP-1 was decreased, but BMPRs were still well-expressed in proliferating chondrocytes. The temporal and spatial expression of BMP and BMPR suggests that BMP and BMP receptors play roles in the multistep cascade of enchondral ossification in the epiphyseal growth plate.

A randomised, phase II study of repeated rhenium-188-HEDP combined with docetaxel and prednisone versus docetaxel and prednisone alone in castration-resistant prostate cancer (CRPC) metastatic to bone; the Taxium II trial.

PubMed

van Dodewaard-de Jong, Joyce M; de Klerk, John M H; Bloemendal, Haiko J; Oprea-Lager, Daniela E; Hoekstra, Otto S; van den Berg, H Pieter; Los, Maartje; Beeker, Aart; Jonker, Marianne A; O'Sullivan, Joe M; Verheul, Henk M W; van den Eertwegh, Alfons J M

2017-08-01

Rhenium-188-HEDP is a beta-emitting radiopharmaceutical used for palliation of metastatic bone pain. We investigated whether the addition of rhenium-188-HEDP to docetaxel/prednisone improved efficacy of chemotherapy in patients with CRPC. Patients with progressive CRPC and osteoblastic bone metastases were randomised for first-line docetaxel 75 mg/m 2 3-weekly plus prednisone with or without 2 injections of rhenium-188-HEDP after the third (40 MBq/kg) and after the sixth (20 MBq/kg) cycle of docetaxel. Primary endpoint was progression-free survival (PFS), defined as either PSA, radiographic or clinical progression. Patients were stratified by extent of bone metastases and hospital. Forty-two patients were randomised for standard treatment and 46 patients for combination therapy. Median number of cycles of docetaxel was 9 in the control group and 8 in the experimental group. Median follow-up was 18.4 months. Two patients from the experimental group did not start treatment after randomisation. In the intention to treat analysis no differences in PFS, survival and PSA became apparent between the two groups. In an exploratory per-protocol analysis median overall survival was significantly longer in the experimental group (33.8 months (95%CI 31.75-35.85)) than in the control group (21.0 months (95%CI 13.61-28.39); p 0.012). Also median PFS in patients with a baseline phosphatase >220U/L was significantly better with combination treatment (9.0 months (95%CI 3.92-14.08) versus 6.2 months (95%CI 3.08-9.32); log rank p 0.005). As expected, thrombocytopenia (grade I/II) was reported more frequently in the experimental group (25% versus 0%). Combined treatment with rhenium-188-HEDP and docetaxel did not prolong PFS in patients with CRPC. The observed survival benefit in the per-protocol analysis warrants further studies in the combined treatment of chemotherapy and radiopharmaceuticals.

[The role of brain-derived neurotrophic factor in pain facilitation and spinal mechanism in rat model of bone cancer pain].

PubMed

Wang, Li-na; Yang, Jian-ping; Ji, Fu-hai; Wang, Xiu-yun; Zuo, Jian-ling; Xu, Qi-nian; Jia, Xiao-ming; Zhou, Jing; Ren, Chun-guang; Li, Wei

2011-05-10

To investigate the role of brain-derived neurotrophic factor (BDNF) in pain facilitation and spinal mechanisms in the rat model of bone cancer pain. The bone cancer pain model was developed by inoculated Walker 256 mammary gland carcinoma cells into the tibia medullary cavity. Sixty SD female rats were divided into 5 groups (n = 12 each) randomly; group I: control group (sham operation); group II: model group; group III: control group + anti-BDNF intrathecal (i.t.); group IV: model group + control IgG i.t.; group V: model group + anti-BDNF i.t.. Anti-BDNF or control IgG was injected i.t. during 7 to 9th day. Von-Frey threshold was measured one day before operation and every 2 days after operation. On the 9th day after threshold tested, rats were sacrificed after i.t. injection of either anti-BDNF or control IgG, the lumbar 4-6 spinal cord was removed. The expression of the spinal BDNF and the phosphorylation of extracellular signal-regulated protein kinase 1/2 (p-ERK1/2) were detected by immunohistochemistry assay and Western-Blot. Co-expression pattern of BDNF and p-ERK1/2 were determined by double-labeling immunofluorescence. We demonstrated the coexistence of BDNF and p-ERK1/2 in the spinal cord of rats. From the 7 to 9th day after operation, von-Frey threshold in groups II and IV was significantly lower than that in group I and group V (P < 0.01), group V was remarkly higher than that in group IV (P < 0.01). The spinal BDNF and p-ERK1/2 expression in group II or IV were significantly increased compared with that in group I or V (P < 0.01), intrathecal anti-BDNF was significantly suppressed BDNF and p-ERK1/2 expression (P < 0.01). BDNF and p-ERK1/2 was coexistence in the spinal cord of rats, and it maybe involved in the bone cancer pain.

Investigation of fatigue crack growth in acrylic bone cement using the acoustic emission technique.

PubMed

Roques, A; Browne, M; Thompson, J; Rowland, C; Taylor, A

2004-02-01

Failure of the bone cement mantle has been implicated in the loosening process of cemented hip stems. Current methods of investigating degradation of the cement mantle in vitro often require sectioning of the sample to confirm failure paths. The present research investigates acoustic emission as a passive experimental method for the assessment of bone cement failure. Damage in bone cement was monitored during four point bending fatigue tests through an analysis of the peak amplitude, duration, rise time (RT) and energy of the events emitted from the damage sections. A difference in AE trends was observed during failure for specimens aged and tested in (i) air and (ii) Ringer's solution at 37 degrees C. It was noted that the acoustic behaviour varied according to applied load level; events of higher duration and RT were emitted during fatigue at lower stresses. A good correlation was observed between crack location and source of acoustic emission, and the nature of the acoustic parameters that were most suited to bone cement failure characterisation was identified. The methodology employed in this study could potentially be used as a pre-clinical assessment tool for the integrity of cemented load bearing implants.

Comparison of Piezosurgery and Conventional Rotary Instruments for Removal of Impacted Mandibular Third Molars: A Randomized Controlled Clinical and Radiographic Trial

PubMed Central

Shokry, Mohamed; Aboelsaad, Nayer

2016-01-01

The purpose of this study was to test the effect of the surgical removal of impacted mandibular third molars using piezosurgery versus the conventional surgical technique on postoperative sequelae and bone healing. Material and Methods. This study was carried out as a randomized controlled clinical trial: split mouth design. Twenty patients with bilateral mandibular third molar mesioangular impaction class II position B indicated for surgical extraction were treated randomly using either the piezosurgery or the conventional bur technique on each site. Duration of the procedure, postoperative edema, trismus, pain, healing, and bone density and quantity were evaluated up to 6 months postoperatively. Results. Test and control sites were compared using paired t-test. There was statistical significance in reduction of pain and swelling in test sites, where the time of the procedure was statistically increased in test site. For bone quantity and quality, statistical difference was found where test site showed better results. Conclusion. Piezosurgery technique improves quality of patient's life in form of decrease of postoperative pain, trismus, and swelling. Furthermore, it enhances bone quality within the extraction socket and bone quantity along the distal aspect of the mandibular second molar. PMID:27597866

A Comparison of More and Less Aggressive Bone Debridement Protocols for the Treatment of Open Supracondylar Femur Fractures

PubMed Central

Ricci, William M.; Collinge, Cory; Streubel, Philipp N.; McAndrew, Christopher M.; Gardner, Michael J.

2014-01-01

Objectives This study compared results of aggressive and nonaggressive debridement protocols for the treatment of high energy open supracondylar femur fractures after the primary procedure, with respect to the requirement for secondary bone grafting procedures, and deep infection. Design Retrospective review Setting Level I and Level II Trauma Centers Patients/Participants Twenty-nine consecutive patients with high grade open (Gustilo Types II and III) supracondylar femur fractures (OTA/AO 33A and C) treated with debridement and locked plating. Intervention Surgeons at two different Level I trauma centers had different debridement protocols for open supracondylar femur fractures. One center used a More Aggressive (MA)protocol in their patients (n=17) that included removal of all devitalized bone and placement of antibiotic cement spacers to fill large segmental defects. The other center used a Less Aggressive (LA) protocol in their patients (n=12) that included debridement of grossly contaminated bone with retention of other bone fragments and no use of antibiotic cement spacers. All other aspects of the treatment protocol at the two centers were similar: definitive fixation with locked plates in all cases; IV antibiotics were used until definitive wound closure; and weight bearing was advanced upon clinical and radiographic evidence of fracture healing. Main Outcome Measurements Healing after the primary procedure, requirement for secondary bone grafting procedures, and the presence of deep infection. Results Demographics were similar between included patients at each center with regard to: age; gender; rate of open fractures; open fracture classification; mechanism; and smoking (p>.05). Patients at the MA center were more often diabetic (p<.05).Cement spacers to fill segmental defects were used more often after MA debridement (35% vs 0%, p<0.006) and more patients had a plan for staged bone grafting after MA debridement (71% vs 8%, p<0.006). Healing after the index fixation procedure occurred more often after LA debridement (92% vs 35%, p<0.003). There was no difference in infection rate between the two protocols: 25% with the LA protocol; and 18% with the MA protocol, (p=0.63). All patients in both groups eventually healed and were without evidence of infection at an average of 1.8 years of follow-up. Conclusion The degree to which bone should be debrided after a high energy, high grade, open supracondylar femur fracture is a matter of surgeon judgment and falls along a continuous spectrum. Based on the results of the current study, the theoretic tradeoff between infection risk and osseous healing potential, seems to favor a less aggressive approach towards bone debridement in the initial treatment. PMID:23760177

A comparison of more and less aggressive bone debridement protocols for the treatment of open supracondylar femur fractures.

PubMed

Ricci, William M; Collinge, Cory; Streubel, Philipp N; McAndrew, Christopher M; Gardner, Michael J

2013-12-01

This study compared results of aggressive and nonaggressive debridement protocols for the treatment of high-energy, open supracondylar femur fractures after the primary procedure, with respect to the requirement for secondary bone grafting procedures, and deep infection. Retrospective review. Level I and level II trauma centers. Twenty-nine consecutive patients with high-grade, open (Gustilo types II and III) supracondylar femur fractures (OTA/AO 33A and C) treated with debridement and locked plating. Surgeons at 2 different level I trauma centers had different debridement protocols for open supracondylar femur fractures. One center used a more aggressive (MA) protocol in their patients (n = 17) that included removal of all devitalized bone and placement of antibiotic cement spacers to fill large segmental defects. The other center used a less aggressive (LA) protocol in their patients (n = 12) that included debridement of grossly contaminated bone with retention of other bone fragments and no use of antibiotic cement spacers. All other aspects of the treatment protocol at the 2 centers were similar: definitive fixation with locked plates in all cases, IV antibiotics were used until definitive wound closure, and weight bearing was advanced upon clinical and radiographic evidence of fracture healing. Healing after the primary procedure, requirement for secondary bone grafting procedures, and the presence of deep infection. Demographics were similar between included patients at each center with regard to age, gender, rate of open fractures, open fracture classification, mechanism, and smoking (P > 0.05). Patients at the MA center were more often diabetic (P < 0.05). Cement spacers to fill segmental defects were used more often after MA debridement (35% vs. 0%, P < 0.006), and more patients had a plan for staged bone grafting after MA debridement (71% vs. 8%, P < 0.006). Healing after the index fixation procedure occurred more often after LA debridement (92% vs. 35%, P < 0.003). There was no difference in infection rate between the 2 protocols: 25% with the LA protocol and 18% with the MA protocol (P = 0.63). All patients in both groups eventually healed and were without evidence of infection at an average of 1.8 years of follow-up. The degree to which bone should be debrided after a high-energy, high-grade, open supracondylar femur fracture is a matter of surgeon judgment and falls along a continuous spectrum. Based on the results of the current study, the theoretic trade-off between infection risk and osseous healing potential seems to favor an LA approach toward bone debridement in the initial treatment. Therapeutic level III.

Veganism and osteoporosis: a review of the current literature.

PubMed

Smith, Annabelle M

2006-10-01

The purpose of this review is to examine the current literature regarding calcium and Vitamin D deficiencies in vegan diets and the possible relationship to low bone mineral density and incidence for fracture. Prominent databases were searched for original research publications providing data capable of answering these questions: (i) Do vegans have lower-than-recommended levels of calcium/Vitamin D? (ii) Do vegans have lower bone mineral density than their non-vegan counterparts? (iii) Are vegans at a greater risk for fractures than non-vegans? The findings gathered consistently support the hypothesis that vegans do have lower bone mineral density than their non-vegan counterparts. However, the evidence regarding calcium, Vitamin D and fracture incidence is inconclusive. More research is needed to definitively answer these questions and to address the effects of such deficiencies on the medical and socioeconomic aspects of life.

Calcified cartilage or bone? Collagens in the tessellated endoskeletons of cartilaginous fish (sharks and rays).

PubMed

Seidel, Ronald; Blumer, Michael; Pechriggl, Elisabeth-Judith; Lyons, Kady; Hall, Brian K; Fratzl, Peter; Weaver, James C; Dean, Mason N

2017-10-01

The primary skeletal tissue in elasmobranchs -sharks, rays and relatives- is cartilage, forming both embryonic and adult endoskeletons. Only the skeletal surface calcifies, exhibiting mineralized tiles (tesserae) sandwiched between a cartilage core and overlying fibrous perichondrium. These two tissues are based on different collagens (Coll II and I, respectively), fueling a long-standing debate as to whether tesserae are more like calcified cartilage or bone (Coll 1-based) in their matrix composition. We demonstrate that stingray (Urobatis halleri) tesserae are bipartite, having an upper Coll I-based 'cap' that merges into a lower Coll II-based 'body' zone, although tesserae are surrounded by cartilage. We identify a 'supratesseral' unmineralized cartilage layer, between tesserae and perichondrium, distinguished from the cartilage core in containing Coll I and X (a common marker for mammalian mineralization), in addition to Coll II. Chondrocytes within tesserae appear intact and sit in lacunae filled with Coll II-based matrix, suggesting tesserae originate in cartilage, despite comprising a diversity of collagens. Intertesseral joints are also complex in their collagenous composition, being similar to supratesseral cartilage closer to the perichondrium, but containing unidentified fibrils nearer the cartilage core. Our results indicate a unique potential for tessellated cartilage in skeletal biology research, since it lacks features believed diagnostic for vertebrate cartilage mineralization (e.g. hypertrophic and apoptotic chondrocytes), while offering morphologies amenable for investigating the regulation of complex mineralized ultrastructure and tissues patterned on multiple collagens. Copyright © 2017 Elsevier Inc. All rights reserved.

Recovery of Spaceflight-induced Bone Loss: Bone Mineral Density after Long-Duration Missions as Fitted with an Exponential Function

NASA Technical Reports Server (NTRS)

Sibonga, J. D.; Evans, H. J.; Sung, H. G.; Spector, E. R.; Lang, T. F.; Oganov, V. S.; Bakulin, A. V.; Shackelford, L. C.; LeBlanc, A. D.

2007-01-01

The loss of bone mineral in NASA astronauts during spaceflight has been investigated throughout the more than 40 years of space travel. Consequently, it is a medical requirement at NASA Johnson Space Center (JSC) that changes in bone mass be monitored in crew members by measuring bone mineral density (BMD) with dual-energy x-ray absorptiometry (DXA) before and after flight on astronauts who serve on long-duration missions (4-6 months). We evaluated this repository of medical data to track whether there is recovery of bone mineral that was lost during spaceflight. Our analysis was supplemented by BMD data from cosmonauts ( by convention, a space traveler formally employed by the Russia Aviation and Space Agency or by the previous Soviet Union) who had also flown on long-duration missions. Data from a total of 45 individual crew members -- a small number of whom flew on more than one mission -- were used in this analysis. Changes in BMD (between 56 different sets of pre- and postflight measurements) were plotted as a function of time (days after landing). Plotted BMD changes were fitted to an exponential mathematical function that estimated: i) BMD change on landing day (day 0) and ii) the number of days after landing when 50% of the lost bone would be recovered ("50% recovery time") in the lumbar spine, trochanter, pelvis, femoral neck and calcaneus. In sum, averaged losses of bone mineral after long-duration spaceflight ranged between 2-9% across all sites with our recovery model predicting a 50% restoration of bone loss for all sites to be within 9 months.

Skeletal Recovery Following Long-Duration Spaceflight Missions as Determined by Preflight and Postflight DXA Scans of 45 Crew Members

NASA Technical Reports Server (NTRS)

Sibonga, J. D.; Evans, H. J.; Sung, H. G.; Spector, E. R.; Lang, T. F.; Oganov, V. S.; Bakulin, A. V.; Shackelford, L. C.; LeBlanc, A. D.

2006-01-01

Introduction: The loss of bone mineral in astronauts during spaceflight has been investigated throughout the more than 40 years of bone research in space. Consequently, it is a medical requirement at NASA that changes in bone mass be monitored in crew members by measurements of bone mineral density (BMD) with dual-energy x-ray absorptiometry (DXA). This report is the first to evaluate medical data to address the recovery of bone mineral that is lost during spaceflight. Methods: DXA scans are performed before and after flight in astronauts who serve on long-duration missions (4-6 months) to ensure that medical standards for flight certification are met, to evaluate the effects of spaceflight and to monitor the restoration to preflight BMD status after return to Earth. Through cooperative agreements with the Russian Space Agency, the Bone and Mineral Lab at NASA Johnson Space Center (Houston, TX), also had access to BMD data from cosmonauts who had flown on long-duration missions yielding data from a total of 45 individual crew members. Changes in BMD (between 56 different sets of pre- and postflight measurements) were plotted as a function of time (days after landing); plotted data were fitted to an exponential mathematical model that determined i) BMD change at day 0 after landing and ii) the number of days after which 50% of the lost bone was recovered ("Recovery Half-Life"). These fits were performed for BMD of the lumbar spine, trochanter, pelvis, femoral neck and calcaneus. Results: In sum, averaged losses of bone mineral after spaceflight ranged between 2-9% for sites in the axial and appendicular skeleton. The fitted postflight BMD values predicted a 50% recovery of bone loss for all sites within 9 months.

The effect of different concentrations of topical ozone administration on bone formation in orthopedically expanded suture in rats

PubMed Central

Ramoglu, Sabri Ilhan; Sonmez, Mehmet Fatih

2016-01-01

Summary Background/objective: The aim of this study was to investigate the effects of different concentrations of ozone (O3) therapy on bone regeneration in response to an expansion of the inter-premaxillary suture in rats. Materials and methods: Forty-eight Wistar rats were randomly divided into four groups (n = 12). In groups I, II, and III, 1ml of O3 at 10, 25, and 40 µg/ml was injected at the premaxillary suture, respectively. In group IV (control group), 1ml of saline solution was injected at the same point during the expansion procedure for 5 days. Bone regeneration in the suture was evaluated histomorphometrically. The area of new bone and fibrotic area, the number of osteoblasts and osteoclasts, and the amount of vascularity were measured and compared. The density of the newly formed bone in the expansion area was measured by using cone beam computed tomography. Data were analyzed using the Kruskal–Wallis one-way analysis of variance and post hoc Student-Newman–Keuls tests. Results: New bone area, fibrotic area, osteoblast and osteoclast numbers, and the amount of vascularity were significantly higher in experimental groups compared with the control group (P < 0.001). The density of newly formed bone (P < 0.001), new bone formation (P = 0.009), number of capillaries (P < 0.001), number of osteoclasts (P = 0.016), and number of osteoblasts (P < 0.001) in the maxillary sutures were highest in the 25 μg/ml O3 group compared with the other experimental groups and control group. Conclusions/implications: The application of O3 therapy can stimulate bone regeneration in an orthopedically expanded inter-premaxillary suture during both the expansion and retention periods. PMID:26136437

Cyclic hydrostatic pressure stimulates enhanced bone development in the foetal chick femur in vitro.

PubMed

Henstock, J R; Rotherham, M; Rose, J B; El Haj, A J

2013-04-01

Mechanical loading of bone and cartilage in vivo results in the generation of cyclic hydrostatic forces as bone compression is transduced to fluid pressure in the canalicular network and the joint synovium. It has therefore been suggested that hydrostatic pressure is an important stimulus by which osteochondral cells and their progenitors sense and respond to mechanical loading in vivo. In this study, hydrostatic pressure regimes of 0-279kPa at 0.005-2Hz were applied to organotypically cultured ex vivo chick foetal femurs (e11) for 1hour per day in a custom designed bioreactor for 14days and bone formation assessed by X-ray microtomography and qualified by histology. We found that the mineralised portion of the developing femur cultured under any cyclic hydrostatic pressure regime was significantly larger and/or denser than unstimulated controls but that constant (non-cycling) hydrostatic pressure had no effect on bone growth. Further experiments showed that the increase in bone formation was directly proportional to stimulation frequency (R(2)=0.917), but independent of the magnitude of the pressure applied, whilst even very low frequencies of stimulation (0.005Hz) had significant effects on bone growth. Expression of Type-II collagen in both epiphyses and diaphysis was significantly upregulated (1.48-fold and 1.95-fold respectively), together with osteogenic genes (osteonectin and osteopontin) and the osteocyte maturation marker CD44. This work demonstrates that cyclic hydrostatic pressure promotes bone growth and mineralisation in a developmental model and supports the hypothesis that hydrostatic forces play an important role in regulating bone growth and remodelling in vivo. Copyright © 2013 Elsevier Inc. All rights reserved.

The processing and characterization of animal-derived bone to yield materials with biomedical applications. Part II: milled bone powders, reprecipitated hydroxyapatite and the potential uses of these materials.

PubMed

Johnson, G S; Mucalo, M R; Lorier, M A; Gieland, U; Mucha, H

2000-11-01

Further studies on the processing and use of animal-bone-derived calcium phosphate materials in biomedical applications are presented. Bone powders sourced either from the direct crushing and milling of bovine, ovine and cervine bone or after being subjected to defatting and acid digestion/NaOH reprecipitation and sodium hypochlorite hydrogen peroxide treatment of animal bones were characterized using Fourier transform infra-red (FTIR) spectroscopy, 13C solid state magic angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy, atomic absorption (AA) and inductively coupled plasma (ICP) spectrometric techniques. Bone powders were trialled for their potential use as a substrate for phosphine coupling and enzyme immobilization as well as a feedstock powder for plasma spraying on titanium metal substrates. Results indicated that enzyme immobilization by phosphine coupling could be successfully achieved on milled cervine bone with the immobilized enzyme retaining some activity. It was found that the presence of impurities normally carried down with the processing of the bone materials (viz., fat and collagen) played an important role in influencing the adsorbency and reactivity of the powders. Plasma spraying studies using reprecipitated bovine-derived powders produced highly adherent coatings on titanium metal, the composition of which was mostly hydroxyapatite (Ca10(PO4)6(OH)2) with low levels of alpha-tricalcium phosphate (alpha-Ca3(PO4)2) and tetracalcium phosphate (Ca4P2O9) also detected. In general, animal derived calcium phosphate materials constitute a potentially cheaper source of calcium phosphate materials for biomedical applications and make use of a largely under-utilized resource from abattoir wastes. Copyright 2000 Kluwer Academic Publishers

Histopathological and biomechanical evaluation of bone healing properties of DBM and DBM-G90 in a rabbit model.

PubMed

Meimandi Parizi, Abdolhamid; Oryan, Ahmad; Haddadi, Shahram; Bigham Sadegh, Amin

2015-01-01

The present study was designed to investigate the effects of DBM and DBM-G90 on bone healing in a rabbit model. Thirty male white albino rabbits were used in this study. An incision was made in all rabbits under general anesthesia directly over the radius in order to expose it. A 10-mm segmental defect was created on the middle portion of each radius. The defects of 10 rabbits (Group I) were filled with DBM Block and Strip (Zimmer, Inc., Warsaw, IN, USA), the defects of 10 rabbits (Group II) were filled with DBM soaked in G90, and the defects of 10 rabbits (Group III/control) were left empty. The rabbits were euthanized at 60 days postoperatively for histopathological and biomechanical evaluation. At the histopathologic level, the defects of the animals in the DBM and DBM-G90 groups showed more advanced healing criteria than those of the control group. In biomechanical findings, there was a statistically significant difference between the injured bones and contralateral normal bones of the control group in terms of measured strength. There was not a statistically significant difference between the treated bones of the DBM and DBM-G90 groups with contralateral normal bones, nor was there a statistically significant difference between the treated bones of the DBM and DBM-G90 groups with the treated bones of the control group, in terms of other biomechanical tests. Based on the histopathological and biomechanical findings, the DBM and DBM-G90 groups demonstrated superior osteogenic potential; however, G90 shows no superiority over DBM on bone healing.

Microarchitecture and Bone Quality in the Human Calcaneus; Local Variations of Fabric Anisotropy

PubMed Central

Souzanchi, M F; Palacio-Mancheno, P E; Borisov, Y; Cardoso, L; Cowin, SC

2012-01-01

The local variability of microarchitecture of human trabecular calcaneus bone is investigated using high resolution microCT scanning. The fabric tensor is employed as the measure of the microarchitecture of the pore structure of a porous medium. It is hypothesized that a fabric tensor-dependent poroelastic ultrasound approach will more effectively predict the data variance than will porosity alone. The specific aims of the present study are i) to quantify the morphology and local anisotropy of the calcaneus microarchitecture with respect to anatomical directions, ii) to determine the interdependence, or lack thereof, of microarchitecture parameters, fabric, and volumetric bone mineral density (vBMD), and iii) to determine the relative ability of vBMD and fabric measurements in evaluating the variance in ultrasound wave velocity measurements along orthogonal directions in the human calcaneus. Our results show that the microarchitecture in the analyzed regions of human calcanei is anisotropic, with a preferred alignment along the posterior-anterior direction. Strong correlation was found between most scalar architectural parameters and vBMD. However, no statistical correlation was found between vBMD and the fabric components, the measures of the pore microstructure orientation. Therefore, among the parameters usually considered for cancellous bone (i.e., classic histomorphometric parameters such as porosity, trabecular thickness, number and separation), only fabric components explain the data variance that cannot be explained by vBMD, a global mass measurement, which lacks the sensitivity and selectivity to distinguish osteoporotic from healthy subjects because it is insensitive to directional changes in bone architecture. This study demonstrates that a multi-directional, fabric-dependent poroelastic ultrasound approach has the capability of characterizing anisotropic bone properties (bone quality) beyond bone mass, and could help to better understand anisotropic changes in bone architecture using ultrasound. PMID:22807141

Transgenic Expression of Osteoactivin/gpnmb Enhances Bone Formation In Vivo and Osteoprogenitor Differentiation Ex Vivo.

PubMed

Frara, Nagat; Abdelmagid, Samir M; Sondag, Gregory R; Moussa, Fouad M; Yingling, Vanessa R; Owen, Thomas A; Popoff, Steven N; Barbe, Mary F; Safadi, Fayez F

2016-01-01

Initial identification of osteoactivin (OA)/glycoprotein non-melanoma clone B (gpnmb) was demonstrated in an osteopetrotic rat model, where OA expression was increased threefold in mutant bones, compared to normal. OA mRNA and protein expression increase during active bone regeneration post-fracture, and primary rat osteoblasts show increased OA expression during differentiation in vitro. To further examine OA/gpnmb as an osteoinductive agent, we characterized the skeletal phenotype of transgenic mouse overexpressing OA/gpnmb under the CMV-promoter (OA-Tg). Western blot analysis showed increased OA/gpnmb in OA-Tg osteoblasts, compared to wild-type (WT). In OA-Tg mouse femurs versus WT littermates, micro-CT analysis showed increased trabecular bone volume and thickness, and cortical bone thickness; histomorphometry showed increased osteoblast numbers, bone formation and mineral apposition rates in OA-Tg mice; and biomechanical testing showed higher peak moment and stiffness. Given that OA/gpnmb is also over-expressed in osteoclasts in OA-Tg mice, we evaluated bone resorption by ELISA and histomorphometry, and observed decreased serum CTX-1 and RANK-L, and decreased osteoclast numbers in OA-Tg, compared to WT mice, indicating decreased bone remodeling in OA-Tg mice. The proliferation rate of OA-Tg osteoblasts in vitro was higher, compared to WT, as was alkaline phosphatase staining and activity, the latter indicating enhanced differentiation of OA-Tg osteoprogenitors. Quantitative RT-PCR analysis showed increased TGF-β1 and TGF-β receptors I and II expression in OA-Tg osteoblasts, compared to WT. Together, these data suggest that OA overexpression has an osteoinductive effect on bone mass in vivo and stimulates osteoprogenitor differentiation ex vivo. © 2015 Wiley Periodicals, Inc.

Post-treatment glenoid classification system for total shoulder arthroplasty.

PubMed

Churchill, R Sean

2012-04-01

Over the past 10 years, numerous advancements in glenoid preparation and resurfacing have occurred. Current glenoid classification systems are either focused solely on the patient's preoperative glenoid bone configuration or on the available glenoid bone stock in revision arthroplasty cases. While these systems provide value in preoperative planning, they fail to properly classify the surgical reconstruction completed. A literature review of common bone preparation methods and sources of glenoid prosthetic failure was performed. Based upon this review, a classification system for grading the status of the glenoid after prosthetic implantation was developed. A 6 category, post-treatment, glenoid classification system is proposed: type 0: no reaming; type I: glenoid reaming into but not through the subchondral bone; type II: glenoid reaming which perforates through <50% of the subchondral bone surface area; type III: glenoid reaming which perforates through >50% of the subchondral bone surface area; type IV: use of structural bone graft; and type V: use of a posterior augmented glenoid prosthesis. Types I-III are further subdivided into subtype A which have 100% bone support of the prosthesis, and subtype B which have a region of unsupported prosthesis. The classification system proposed addresses the surgical management of the glenoid during prosthetic replacement. This unique approach to classifying the glenoid following surgical intervention will allow direct follow-up comparison of similarly treated glenoid replacements. Future multicenter studies, possibly through joint registry databases, could then determine the long-term efficacy of the various glenoid preparation methods. Copyright © 2012 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

The in vivo behaviour of a sol-gel glass and a glass-ceramic during critical diaphyseal bone defects healing.

PubMed

Gil-Albarova, Jorge; Salinas, Antonio J; Bueno-Lozano, Antonio L; Román, Jesus; Aldini-Nicolo, Nicolo; García-Barea, Agustina; Giavaresi, Gianluca; Fini, Milena; Giardino, Roberto; Vallet-Regí, Maria

2005-07-01

The in vivo evaluation, in New Zealand rabbits, of a sol-gel glass 70% CaO-30% SiO2 (in mol%) and a glass-ceramic obtained from thermal treatment of the glass, both bioactive in Kokubo's simulated body fluid (SBF), is presented. Femoral bone diaphyseal critical defects were filled with: (i) sol-gel glass cylinders, (ii) glass-ceramic cylinders, or (iii) no material (control group). Osteosynthesis was done by means of anterior screwed plates with an associate intramedullar Kirschner wire. Each group included 10 mature rabbits, 9 months old. Follow-up was 6 months. After sacrifice, macroscopic study showed healing of bone defects, with bone coating over the cylinders, but without evidence of satisfactory repair in control group. Radiographic study showed good implant stability and periosteal growth and bone remodelling around and over the filled bone defect. The morphometric study showed minimum evidences of degradation or resorption in glass-ceramic cylinders, maintaining its original shape, but sol-gel glass cylinders showed abundant fragmentation and surface resorption. An intimate union of the new-formed bone to both materials was observed. Mechanical study showed the higher results in the glass-ceramic group, whereas sol-gel glass and control group showed no differences. The minimum degradation of glass-ceramic cylinders suggests their application in critical bone defects locations of transmission forces or load bearing. The performance of sol-gel glass cylinders suggests their usefulness in locations where a quick resorption should be preferable, considering the possibility of serving as drug or cells vehicle for both of them.

Stem cells and bone: a historical perspective.

PubMed

Bianco, Paolo

2015-01-01

Bone physiology and stem cells were tightly intertwined with one another, both conceptually and experimentally, long before the current explosion of interest in stem cells and so-called regenerative medicine. Bone is home to the two best known and best characterized systems of postnatal stem cells, and it is the only organ in which two stem cells and their dependent lineages coordinate the overall adaptive responses of two major physiological systems. All along, the nature and the evolutionary significance of the interplay of bone and hematopoiesis have remained a major scientific challenge, but also allowed for some of the most spectacular developments in cell biology-based medicine, such as hematopoietic stem cell transplantation. This question recurs in novel forms at multiple turning points over time: today, it finds in the biology of the "niche" its popular phrasing. Entirely new avenues of investigation emerge as a new view of bone in physiology and medicine is progressively established. Looking at bone and stem cells in a historical perspective provides a unique case study to highlight the general evolution of science in biomedicine since the end of World War II to the present day. A paradigm shift in science and in its relation to society and policies occurred in the second half of the XXth century, with major implications thereof for health, industry, drug development, market and society. Current interest in stem cells in bone as in other fields is intertwined with that shift. New opportunities and also new challenges arise. This article is part of a Special Issue entitled "Stem cells and bone". Copyright © 2014. Published by Elsevier Inc.

Bone density and size in ambulatory children with cerebral palsy.

PubMed

Al Wren, Tishya; Lee, David C; Kay, Robert M; Dorey, Frederick J; Gilsanz, Vicente

2011-02-01

To examine the relation of axial and appendicular bone properties in ambulatory children with cerebral palsy (CP) to functional (Gross Motor Function Classification System [GMFCS]) level. Quantitative computed tomography measurements were compared among 37 children with CP (12 children in GMFCS level I, five in level II, 18 in level III, two in level IV; five with hemiplegia, 23 with diplegia, two with triplegia, seven with quadriplegia; mean age 9y 4mo, SD 1y 6mo; 18 males, 19 females) and 37 children in a comparison group (same age and sex distributions). Linear regression was used to evaluate differences in volumetric cancellous bone density (vBMD) and geometric properties of the L3 vertebra and tibia, adjusting for height, weight, and sex as covariates. The comparison group had larger vertebrae than the children with CP (p = 0.02) owing to smaller vertebral size in GMFCS levels III and IV, but there was no difference in vertebral vBMD (p = 0.49). In the tibia, bone volumetric density (p = 0.09) and size (p = 0.02) decreased with increasing GMFCS level. GMFCS level had a greater effect on bone size in females than in males (p<0.07). Children with CP of all levels may have less bone in their tibias, whereas spine deficits differentially affect more involved children. Because even small bone deficits may manifest as osteoporosis later in life, it is important to study bone acquisition in all children with CP. © The Authors. Journal compilation © Mac Keith Press 2010.

The role of cyclase activating (CAP) and cyclase inhibiting (CIP) parathormone fractions in the assessment of bone metabolism disturbances in women with hyperprolactinemia of various origin.

PubMed

Zadrozna-Sliwka, Beata; Bolanowski, Marek; Jawiarczyk, Aleksandra; Kaluzny, Marcin; Syrycka, Joanna

2008-02-01

Hyperprolactinemia could be one of possible causes of bone loss. The reason is thought to be connected with hypogonadism due to PRL excess and the role of other hormones like PTH and PTH-rP. There is no data on the influence of PTH fractions (CAP and CIP) on bone turnover and density in hyperprolactinemia. The aim of the study was to assess the influence of PTH and its fractions on bone metabolism in hyperprolactinemia of various origin. The study was carried out in 75 women. Group I consisted of 32 women with prolactinoma, group II consisted of 43 women with functional hyperprolactinemia. Both groups were subdivided in patients with hypogonadism and normal gonadal function. The control group consisted of 29 healthy women. In all subjects PRL, PTH and its fractions (CAP, CIP), and bone turnover markers (BAP, ICTP) were studied. BMD measurement was carried out using DXA. In patients with functional hyperprolactinemia i-PTH and CAP levels were lower than in controls. CIP concentrations were lower in patients than in controls. CAP/CIP ratio was higher in patients with prolactinoma than in patients with functional hyperprolactinemia and controls. Higher values of bone turnover markers (BAP, ICTP) in patients groups and subgroups were shown as compared to controls. Some correlations between PTH and its fractions, and BMD and bone turnover were observed. There is no direct benefit from the assessment of parathormone fractions and CAP/CIP ratio in the prognosis of bone metabolism changes in hyperprolactinemia of various origin.

[Influence of preoperative bone mass density in periprosthetic bone remodeling after implantation of ABG-II prosthesis: A 10-year follow-up].

PubMed

Aguilar Ezquerra, A; Panisello Sebastiá, J J; Mateo Agudo, J

2016-01-01

Preoperative bone mass index has shown to be an important factor in peri-prosthetic bone remodelling in short follow-up studies. Bone density scans (DXA) were used to perform a 10-year follow-up study of 39 patients with a unilateral, uncemented hip replacement. Bone mass index measurements were made at 6 months, one year, 3 years, 5 years, and 10 years after surgery. Pearson coefficient was used to quantify correlations between preoperative bone mass density (BMD) and peri-prosthetic BMD in the 7 Gruen zones at 6 months, one year, 3 years, 5 years, and 10 years. Pre-operative BMD was a good predictor of peri-prosthetic BMD one year after surgery in zones 1, 2, 4, 5 and 6 (Pearson index from 0.61 to 0.75). Three years after surgery it has good predictive power in zones 1, 4 and 5 (0.71-0.61), although in zones 3 and 7 low correlation was observed one year after surgery (0.51 and 0.57, respectively). At the end of the follow-up low correlation was observed in the 7 Gruen zones. Sex and BMI were found to not have a statistically significant influence on peri-prosthetic bone remodelling. Although preoperative BMD seems to be an important factor in peri-prosthetic remodelling one year after hip replacement, it loses its predictive power progressively, until not being a major factor in peri-prosthetic remodelling ten years after surgery. Copyright © 2015 SECOT. Published by Elsevier Espana. All rights reserved.

CYTOGENETIC STUDIES OF THREE TRIAZINE HERBICIDES II. IN VIVO MICRONUCLEUS STUDIES IN MOUSE BONE MARROW

EPA Science Inventory

Atrazine, simazine, and cyanazine are widely used preemergence and postemergence triazine herbicides that have made their way into the potable water supply of many agricultural communities. There are several contradictory studies in the literature. Our previous in vitro studies...

21 CFR 866.5490 - Hemopexin immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... survival of mature red blood cells and inability of the bone marrow to compensate for their decreased life span) and sickle cell anemia. (b) Classification. Class II (special controls). The device is exempt... Hemopexin immunological test system. (a) Indentification. A hemopexin immunological test system is a device...

21 CFR 866.5490 - Hemopexin immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... survival of mature red blood cells and inability of the bone marrow to compensate for their decreased life span) and sickle cell anemia. (b) Classification. Class II (special controls). The device is exempt... Hemopexin immunological test system. (a) Indentification. A hemopexin immunological test system is a device...

21 CFR 866.5490 - Hemopexin immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... survival of mature red blood cells and inability of the bone marrow to compensate for their decreased life span) and sickle cell anemia. (b) Classification. Class II (special controls). The device is exempt... Hemopexin immunological test system. (a) Indentification. A hemopexin immunological test system is a device...

21 CFR 866.5490 - Hemopexin immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... survival of mature red blood cells and inability of the bone marrow to compensate for their decreased life span) and sickle cell anemia. (b) Classification. Class II (special controls). The device is exempt... Hemopexin immunological test system. (a) Indentification. A hemopexin immunological test system is a device...

Porous titanium and Ti-35Nb alloy: effects on gene expression of osteoblastic cells derived from human alveolar bone.

PubMed

do Prado, Renata Falchete; Rabêlo, Sylvia Bicalho; de Andrade, Dennia Perez; Nascimento, Rodrigo Dias; Henriques, Vinicius André Rodrigues; Carvalho, Yasmin Rodarte; Cairo, Carlos Alberto Alves; de Vasconcellos, Luana Marotta Reis

2015-11-01

Tests on titanium alloys that possess low elastic modulus, corrosion resistance and minimal potential toxicity are ongoing. This study aimed to evaluate the behavior of human osteoblastic cells cultured on dense and porous Titanium (Ti) samples comparing to dense and porous Ti-35 Niobium (Ti-35Nb) samples, using gene expression analysis. Scanning electronic microscopy confirmed surface porosity and pore interconnectivity and X-ray diffraction showed titanium beta-phase stabilization in Ti-35Nb alloy. There were no differences in expression of transforming growth factor-β, integrin-β1, alkaline phosphatase, osteopontin, macrophage colony stimulating factor, prostaglandin E synthase, and apolipoprotein E regarding the type of alloy, porosity and experimental period. The experimental period was a significant factor for the markers: bone sialoprotein II and interleukin 6, with expression increasing over time. Porosity diminished Runt-related transcription factor-2 (Runx-2) expression. Cells adhering to the Ti-35Nb alloy showed statistically similar expression to those adhering to commercially pure Ti grade II, for all the markers tested. In conclusion, the molecular mechanisms of interaction between human osteoblasts and the Ti-35Nb alloy follow the principal routes of osseointegration of commercially pure Ti grade II. Porosity impaired the route of transcription factor Runx-2.

Limb bone morphology, bone strength, and cursoriality in lagomorphs

PubMed Central

Young, Jesse W; Danczak, Robert; Russo, Gabrielle A; Fellmann, Connie D

2014-01-01

The primary aim of this study is to broadly evaluate the relationship between cursoriality (i.e. anatomical and physiological specialization for running) and limb bone morphology in lagomorphs. Relative to most previous studies of cursoriality, our focus on a size-restricted, taxonomically narrow group of mammals permits us to evaluate the degree to which ‘cursorial specialization’ affects locomotor anatomy independently of broader allometric and phylogenetic trends that might obscure such a relationship. We collected linear morphometrics and μCT data on 737 limb bones covering three lagomorph species that differ in degree of cursoriality: pikas (Ochotona princeps, non-cursorial), jackrabbits (Lepus californicus, highly cursorial), and rabbits (Sylvilagus bachmani, level of cursoriality intermediate between pikas and jackrabbits). We evaluated two hypotheses: cursoriality should be associated with (i) lower limb joint mechanical advantage (i.e. high ‘displacement advantage’, permitting more cursorial species to cycle their limbs more quickly) and (ii) longer, more gracile limb bones, particularly at the distal segments (as a means of decreasing rotational inertia). As predicted, highly cursorial jackrabbits are typically marked by the lowest mechanical advantage and the longest distal segments, non-cursorial pikas display the highest mechanical advantage and the shortest distal segments, and rabbits generally display intermediate values for these variables. Variation in long bone robusticity followed a proximodistal gradient. Whereas proximal limb bone robusticity declined with cursoriality, distal limb bone robusticity generally remained constant across the three species. The association between long, structurally gracile limb bones and decreased maximal bending strength suggests that the more cursorial lagomorphs compromise proximal limb bone integrity to improve locomotor economy. In contrast, the integrity of distal limb bones is maintained with increasing cursoriality, suggesting that the safety factor takes priority over locomotor economy in those regions of the postcranial skeleton that experience higher loading during locomotion. Overall, these findings support the hypothesis that cursoriality is associated with a common suite of morphological adaptations across a range of body sizes and radiations. PMID:25046350

Is trabecular bone permeability governed by molecular ordering-induced fluid viscosity gain? Arguments from re-evaluation of experimental data in the framework of homogenization theory.

PubMed

Abdalrahman, T; Scheiner, S; Hellmich, C

2015-01-21

It is generally agreed on that trabecular bone permeability, a physiologically important quantity, is governed by the material׳s (vascular or intertrabecular) porosity as well as by the viscosity of the pore-filling fluids. Still, there is less agreement on how these two key factors govern bone permeability. In order to shed more light onto this somewhat open issue, we here develop a random homogenization scheme for upscaling Poiseuille flow in the vascular porosity, up to Darcy-type permeability of the overall porous medium "trabecular bone". The underlying representative volume element of the macroscopic bone material contains two types of phases: a spherical, impermeable extracellular bone matrix phase interacts with interpenetrating cylindrical pore channel phases that are oriented in all different space directions. This type of interaction is modeled by means of a self-consistent homogenization scheme. While the permeability of the bone matrix equals to zero, the permeability of the pore phase is found through expressing the classical Hagen-Poiseuille law for laminar flow in the format of a "micro-Darcy law". The upscaling scheme contains pore size and porosity as geometrical input variables; however, they can be related to each other, based on well-known relations between porosity and specific bone surface. As two key results, validated through comprehensive experimental data, it appears (i) that the famous Kozeny-Carman constant (which relates bone permeability to the cube of the porosity, the square of the specific surface, as well as to the bone fluid viscosity) needs to be replaced by an again porosity-dependent rational function, and (ii) that the overall bone permeability is strongly affected by the pore fluid viscosity, which, in case of polarized fluids, is strongly increased due to the presence of electrically charged pore walls. Copyright © 2014 Elsevier Ltd. All rights reserved.

Small subchondral drill holes improve marrow stimulation of articular cartilage defects.

PubMed

Eldracher, Mona; Orth, Patrick; Cucchiarini, Magali; Pape, Dietrich; Madry, Henning

2014-11-01

Subchondral drilling is an established marrow stimulation technique. Osteochondral repair is improved when the subchondral bone is perforated with small drill holes, reflecting the physiological subchondral trabecular distance. Controlled laboratory study. A rectangular full-thickness chondral defect was created in the trochlea of adult sheep (n = 13) and treated with 6 subchondral drillings of either 1.0 mm (reflective of the trabecular distance) or 1.8 mm in diameter. Osteochondral repair was assessed after 6 months in vivo by macroscopic, histological, and immunohistochemical analyses and by micro-computed tomography. The application of 1.0-mm subchondral drill holes led to significantly improved histological matrix staining, cellular morphological characteristics, subchondral bone reconstitution, and average total histological score as well as significantly higher immunoreactivity to type II collagen and reduced immunoreactivity to type I collagen in the repair tissue compared with 1.8-mm drill holes. Analysis of osteoarthritic changes in the cartilage adjacent to the defects revealed no significant differences between treatment groups. Restoration of the microstructure of the subchondral bone plate below the chondral defects was significantly improved after 1.0-mm compared to 1.8-mm drilling, as shown by higher bone volume and reduced thickening of the subchondral bone plate. Likewise, the microarchitecture of the drilled subarticular spongiosa was better restored after 1.0-mm drilling, indicated by significantly higher bone volume and more and thinner trabeculae. Moreover, the bone mineral density of the subchondral bone in 1.0-mm drill holes was similar to the adjacent subchondral bone, whereas it was significantly reduced in 1.8-mm drill holes. No significant correlations existed between cartilage and subchondral bone repair. Small subchondral drill holes that reflect the physiological trabecular distance improve osteochondral repair in a translational model more effectively than larger drill holes. These results have important implications for the use of subchondral drilling for marrow stimulation, as they support the use of small-diameter bone-cutting devices. © 2014 The Author(s).

Clinical application of bone morphogenetic proteins for bone healing: a systematic review.

PubMed

Krishnakumar, Gopal Shankar; Roffi, Alice; Reale, Davide; Kon, Elizaveta; Filardo, Giuseppe

2017-06-01

This paper documents the existing evidence on bone morphogenetic proteins (BMPs) use for the treatment of bone fractures, non-union, and osteonecrosis, through a review of the clinical literature, underlying potential and limitations in terms of cost effectiveness and risk of complications. A systematic review was performed on the PubMed database using the following string: (bone morphogenetic proteins OR BMPs) and (bone repair OR bone regeneration) including papers from 2000 to 2016. The search focused on clinical trials dealing with BMPs application to favor bone regeneration in bone fractures, non-union, and osteonecrosis, in English language, with level of evidence I, II, III, and IV. Relevant data (type of study, number of patients, BMPs delivery material, dose, site, follow-up, outcome, and adverse events) were extracted and analyzed. Forty-four articles met the inclusion criteria: 10 randomized controlled trials (RCTs), 7 comparative studies, 18 case series, and 9 case reports. rhBMP-2 was documented mainly for the treatment of fractures, and rhBMP-7 mainly for non-unions and osteonecrosis. Mixed results were found among RCTs and comparative papers: 11 reported positive results for BMPs augmentation, 3 obtained no significant effects, and 2 showed negative results. The only study comparing the two BMPs showed a better outcome with rhBMP-2 for non-union treatment. Clinical evidence on BMPs use for the treatment of fractures, non-union, and osteonecrosis is still controversial, with the few available reports being mainly of low quality. While positive findings have been described in many studies, mixed results are still present in the literature in terms of efficacy and adverse events. The difficulties in drawing clear conclusions are also due to the studies heterogeneity, mainly in terms of different BMPs applied, with different concomitant treatments for each bone pathology. Therefore, further research with well-designed studies is needed in order to understand the real potential of this biological approach to favour bone healing.

Technical Modifications for Intraoral Quadrangular Le Fort II Osteotomy.

PubMed

Klug, Clemens; Cede, Julia

2017-02-01

The intraoral quadrangular Le Fort II osteotomy (IQLFIIO) represents a reliable surgical method in cases of midfacial deficiency with good functional, esthetic, and stable long-term results. In this technical note, we present 3 surgical modifications to previous reports: 1) inferior orbital rim osteotomy by angulated piezosurgical instruments, thereby avoiding the use of chisels in the orbital region; 2) osteosynthetic fixation only laterally at the zygomatic buttress with 2 L-shaped miniplates, thus avoiding paranasal osteosynthesis; and 3) advancement step camouflage in the lateral infraorbital region with a compound mass of autologous bone chips and fibrin glue with the intention to reduce bone block-associated side effects. Thirteen consecutive patients presenting with midfacial deficiency and Class III malocclusion were treated by IQLFIIO and mandibular osteotomy. In all cases, osteotomy and consecutive down fracture could be conducted as planned using the piezotome. No atypical fractures were encountered. No cases of infraorbital nerve anesthesia developed. Midfacial hypesthesia was found in 54% of the operated sides after 3 months, in 23% after 6 months, and in 13% after 12 months. The 5-month postoperative 3-dimensional scans revealed osseous healing at the infraorbital advancement step. Our results suggest that IQLFIIO can be conducted fully without chisels in the orbital region. Implementation of piezosurgery in IQLFIIO allows for safe bone cutting in the orbital region. Two miniplates and step camouflage with fibrin glue-stabilized bone chips were sufficient for osseous healing. Future studies will focus on quantitative soft to hard tissue changes that occur with IQLFIIO advancement. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

The AO Pediatric Comprehensive Classification of Long Bone Fractures (PCCF).

PubMed

Joeris, Alexander; Lutz, Nicolas; Blumenthal, Andrea; Slongo, Theddy; Audigé, Laurent

2017-04-01

Background and purpose - To achieve a common understanding when dealing with long bone fractures in children, the AO Pediatric Comprehensive Classification of Long Bone Fractures (AO PCCF) was introduced in 2007. As part of its final validation, we present the most relevant fracture patterns in the upper extremities of a representative population of children classified according to the PCCF. Patients and methods - We included children and adolescents (0-17 years old) diagnosed with 1 or more long bone fractures between January 2009 and December 2011 at the university hospitals in Bern and Lausanne (Switzerland). Patient charts were retrospectively reviewed and fractures were classified from standard radiographs. Results - Of 2,292 upper extremity fractures in 2,203 children and adolescents, 26% involved the humerus and 74% involved the forearm. In the humerus, 61%, and in the forearm, 80% of single distal fractures involved the metaphysis. In adolescents, single humerus fractures were more often epiphyseal and diaphyseal fractures, and among adolescents radius fractures were more often epiphyseal fractures than in other age groups. 47% of combined forearm fractures were distal metaphyseal fractures. Only 0.7% of fractures could not be classified within 1 of the child-specific fracture patterns. Of the single epiphyseal fractures, 49% were Salter-Harris type-II (SH II) fractures; of these, 94% occurred in schoolchildren and adolescents. Of the metaphyseal fractures, 58% showed an incomplete fracture pattern. 89% of incomplete fractures affected the distal radius. Of the diaphyseal fractures, 32% were greenstick fractures. 24 Monteggia fractures occurred in pre-school children and schoolchildren, and 2 occurred in adolescents. Interpretation - The pattern of pediatric fractures in the upper extremity can be comprehensively described according to the PCCF. Prospective clinical studies are needed to determine its clinical relevance for treatment decisions and prognostication of outcome.

Regulation of osteoarthritis by omega-3 (n-3) polyunsaturated fatty acids in a naturally occurring model of disease

PubMed Central

Knott, L.; Avery, N.C.; Hollander, A.P.; Tarlton, J.F.

2011-01-01

Summary Objective To examine effects of high omega-3 (n-3) polyunsaturated fatty acid (PUFA) diets on development of osteoarthritis (OA) in a spontaneous guinea pig model, and to further characterise pathogenesis in this model. Modern diets low in n-3 PUFAs have been linked with increases in inflammatory disorders, possibly including OA. However, n-3 is also thought to increases bone density, which is a possible contributing factor in OA. Therefore we aim to determine the net influence of n-3 in disease development. Method OA-prone Dunkin-Hartley (DH) Guinea pigs were compared with OA-resistant Bristol Strain-2s (BS2) each fed a standard or an n-3 diet from 10 to 30 weeks (10/group). We examined cartilage and subchondral bone pathology by histology, and biochemistry, including collagen cross-links, matrix metalloproteinases (MMPs), alkaline phosphatase, glycosaminoglycan (GAG), and denatured type II collagen. Results Dietary n-3 reduced disease in OA-prone animals. Most cartilage parameters were modified by n-3 diet towards those seen in the non-pathological BS2 strain – significantly active MMP-2, lysyl-pyridinoline and total collagen cross-links – the only exception being pro MMP-9 which was lower in the BS2, yet increased with n-3. GAG content was higher and denatured type II lower in the n-3 group. Subchondral bone parameters in the DH n-3 group also changed towards those seen in the non-pathological strain, significantly calcium:phosphate ratios and epiphyseal bone density. Conclusion Dietary n-3 PUFA reduced OA in the prone strain, and most disease markers were modified towards those of the non-OA strain, though not all significantly so. Omega-3 did not increase markers of pathology in either strain. PMID:21723952

A novel whole tooth-in-jaw-bone culture of rat molars: morphological, immunohistochemical, and laser capture microdissection analysis.

PubMed

Chokechanachaisakul, Uraiwan; Kaneko, Tomoatsu; Yamanaka, Yusuke; Okiji, Takashi; Suda, Hideaki

2012-10-01

In conventional whole-tooth culture systems, limitation exists regarding maintenance of the vitality of the dental pulp, because this tissue is encased in rigid dentin walls that hinder nutrition supply. We here report a whole tooth-in-jaw-bone culture system of rat mandibular first molars, where transcardiac perfusion with culture medium was carried out before placement of the jaw bone into culture medium, aiming to facilitate longer time preservation of the dental pulp tissue. Following 7 days of culture, the pulp tissues were analyzed by histology and immunohistochemistry to ED2 (antiresident macrophage). ED2-positive macrophages were also analyzed for their Class II MHC, interleukin-6 (IL-6), and p53 mRNA expression levels by means of immune-laser capture microdissection (immune-LCM). Dentin sialophosphoprotein (DSPP) mRNA expression in odontobalstic layer was also examined by LCM. Teeth cultured following saline-perfusion and nonperfusion served as cultured controls. Normal teeth also served as noncultured controls. Histological examination demonstrated that the structure of the pulp tissue was well preserved in the medium-perfused explants in contrast to the cultured control groups. The Class II MHC, IL-6, and p53 mRNA expression levels of ED2-positive cells and DSPP expression levels of odontoblastic layer tissues in the pulp of medium-perfused explants were not significantly different from those in the noncultured normal teeth. In conclusion, the structural integrity and mRNA expression in the pulp were maintained at the in vivo level in the ex vivo whole tooth-in-jaw-bone culture system. The system may lay the foundation for studies aiming at defining further histological and molecular mechanism of the pulp. Copyright © 2012 Wiley Periodicals, Inc.

Effect of single- and double-row rotator cuff repair at the tendon-to-bone interface: preliminary results using an in vivo sheep model.

PubMed

Baums, M H; Schminke, B; Posmyk, A; Miosge, N; Klinger, H-M; Lakemeier, S

2015-01-01

The clinical superiority of the double-row technique is still a subject of controversial debate in rotator cuff repair. We hypothesised that the expression of different collagen types will differ between double-row and single-row rotator cuff repair indicating a faster healing response by the double-row technique. Twenty-four mature female sheep were randomly assembled to two different groups in which a surgically created acute infraspinatus tendon tear was fixed using either a modified single- or double-row repair technique. Shoulder joints from female sheep cadavers of identical age, bone maturity, and weight served as untreated control cluster. Expression of type I, II, and III collagen was observed in the tendon-to-bone junction along with recovering changes in the fibrocartilage zone after immunohistological tissue staining at 1, 2, 3, 6, 12, and 26 weeks postoperatively. Expression of type III collagen remained positive until 6 weeks after surgery in the double-row group, whereas it was detectable for 12 weeks in the single-row group. In both groups, type I collagen expression increased after 12 weeks. Type II collagen expression was increased after 12 weeks in the double-row versus single-row group. Clusters of chondrocytes were only visible between week 6 and 12 in the double-row group. The study demonstrates differences regarding the expression of type I and type III collagen in the tendon-to-bone junction following double-row rotator cuff repair compared to single-row repair. The healing response in this acute repair model is faster in the double-row group during the investigated healing period.

Periodontal regeneration around natural teeth.

PubMed

Garrett, S

1996-11-01

1. Evidence is conclusive (Table 2) that periodontal regeneration in humans is possible following the use of bone grafts, guided tissue regeneration procedures, both without and in combination with bone grafts, and root demineralization procedures. 2. Clinically guided tissue regeneration procedures have demonstrated significant positive clinical change beyond that achieved with debridement alone in treating mandibular and maxillary (buccal only) Class II furcations. Similar data exist for intraosseous defects. Evidence suggests that the use of bone grafts or GTR procedures produce equal clinical benefit in treating intraosseous defects. Further research is necessary to evaluate GTR procedures compared to, or combined with, bone grafts in treating intraosseous defects. 3. Although there are some data suggesting hopeful results in Class II furcations, the clinical advantage of procedures combining present regenerative techniques remains to be demonstrated. Additional randomized controlled trials with sufficient power are needed to demonstrate the potential usefulness of these techniques. 4. Outcomes following regenerative attempts remain somewhat variable with differences in results between studies and individual subjects. Some of this variability is likely patient related in terms of compliance with plaque control and maintenance procedures, as well as personal habits; e.g., smoking. Variations in the defects selected for study may also affect predictability of outcomes along with other factors. 5. There is evidence to suggest that present regenerative techniques lead to significant amounts of regeneration at localized sites on specific teeth. However, if complete regeneration is to become a reality, additional stimuli to enhance the regenerative process are likely needed. Perhaps this will be accomplished in the future, with combined procedures that include appropriate polypeptide growth factors or tissue factors to provide additional stimulus.

The AO Pediatric Comprehensive Classification of Long Bone Fractures (PCCF)

PubMed Central

Joeris, Alexander; Lutz, Nicolas; Blumenthal, Andrea; Slongo, Theddy; Audigé, Laurent

2017-01-01

Background and purpose To achieve a common understanding when dealing with long bone fractures in children, the AO Pediatric Comprehensive Classification of Long Bone Fractures (AO PCCF) was introduced in 2007. As part of its final validation, we present the most relevant fracture patterns in the upper extremities of a representative population of children classified according to the PCCF. Patients and methods We included children and adolescents (0–17 years old) diagnosed with 1 or more long bone fractures between January 2009 and December 2011 at the university hospitals in Bern and Lausanne (Switzerland). Patient charts were retrospectively reviewed and fractures were classified from standard radiographs. Results Of 2,292 upper extremity fractures in 2,203 children and adolescents, 26% involved the humerus and 74% involved the forearm. In the humerus, 61%, and in the forearm, 80% of single distal fractures involved the metaphysis. In adolescents, single humerus fractures were more often epiphyseal and diaphyseal fractures, and among adolescents radius fractures were more often epiphyseal fractures than in other age groups. 47% of combined forearm fractures were distal metaphyseal fractures. Only 0.7% of fractures could not be classified within 1 of the child-specific fracture patterns. Of the single epiphyseal fractures, 49% were Salter-Harris type-II (SH II) fractures; of these, 94% occurred in schoolchildren and adolescents. Of the metaphyseal fractures, 58% showed an incomplete fracture pattern. 89% of incomplete fractures affected the distal radius. Of the diaphyseal fractures, 32% were greenstick fractures. 24 Monteggia fractures occurred in pre-school children and schoolchildren, and 2 occurred in adolescents. Interpretation The pattern of pediatric fractures in the upper extremity can be comprehensively described according to the PCCF. Prospective clinical studies are needed to determine its clinical relevance for treatment decisions and prognostication of outcome. PMID:27882802

Velocities of Bone Mineral Accrual in Black and White American Children

PubMed Central

Hui, Siu L; Perkins, Anthony J; Harezlak, Jaroslaw; Peacock, Munro; McClintock, Cindy L; Johnston, C Conrad

2010-01-01

Black adults have higher bone mass than whites in the United States, but it is not clear when black children gain bone mineral faster than white children. We performed a cohort study to compare the growth velocity of total-body bone mineral content (TBMC) between black and white children of the same sex at different ages and stages of sexual maturity. TBMC and total-body area were measured in a cohort of 188 black and white boys and girls aged 5 to 15 years annually for up to 4 years. Rates of change in TBMC and area were found to vary with age and with Tanner stage. For both TBMC and area, growth velocities between black and white children differed significantly across Tanner stages. Age-specific velocities were higher in black children during prepuberty and initial entry into puberty but reversed in subsequent Tanner stages. Despite earlier entry into each Tanner stage, black children spent only an average of only 0.2 year longer in Tanner stages II through IV, and total gain in TBMC from age 5 to 15 was not higher in whites. In conclusion, the higher bone mass in black adults compared with whites cannot be attributed to faster accrual during puberty. It is due to black children's higher rate of bone mineral accrual in prepuberty and plausibly in postpuberty. Most of the racial difference in TBMC velocity can be explained by growth in size. © 2010 American Society for Bone and Mineral Research. PMID:20200959

Individual-specific multi-scale finite element simulation of cortical bone of human proximal femur

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

Ascenzi, Maria-Grazia, E-mail: mgascenzi@mednet.ucla.edu; Kawas, Neal P., E-mail: nealkawas@ucla.edu; Lutz, Andre, E-mail: andre.lutz@hotmail.de

2013-07-01

We present an innovative method to perform multi-scale finite element analyses of the cortical component of the femur using the individual’s (1) computed tomography scan; and (2) a bone specimen obtained in conjunction with orthopedic surgery. The method enables study of micro-structural characteristics regulating strains and stresses under physiological loading conditions. The analysis of the micro-structural scenarios that cause variation of strain and stress is the first step in understanding the elevated strains and stresses in bone tissue, which are indicative of higher likelihood of micro-crack formation in bone, implicated in consequent remodeling or macroscopic bone fracture. Evidence that micro-structuremore » varies with clinical history and contributes in significant, but poorly understood, ways to bone function, motivates the method’s development, as does need for software tools to investigate relationships between macroscopic loading and micro-structure. Three applications – varying region of interest, bone mineral density, and orientation of collagen type I, illustrate the method. We show, in comparison between physiological loading and simple compression of a patient’s femur, that strains computed at the multi-scale model’s micro-level: (i) differ; and (ii) depend on local collagen-apatite orientation and degree of calcification. Our findings confirm the strain concentration role of osteocyte lacunae, important for mechano-transduction. We hypothesize occurrence of micro-crack formation, leading either to remodeling or macroscopic fracture, when the computed strains exceed the elastic range observed in micro-structural testing.« less

Selective reduction in cortical bone mineral density in turner syndrome independent of ovarian hormone deficiency.

PubMed

Bakalov, Vladimir K; Axelrod, Lauren; Baron, Jeffrey; Hanton, Lori; Nelson, Lawrence M; Reynolds, James C; Hill, Suvimol; Troendle, James; Bondy, Carolyn A

2003-12-01

Women with Turner syndrome (TS) are at risk for osteoporosis from ovarian failure and possibly from haploinsufficiency for bone-related X-chromosome genes. To establish whether cortical or trabecular bone is predominantly affected, and to control for the ovarian failure, we studied forearm bone mineral density (BMD) in 41 women with TS ages 18-45 yr and in 35 age-matched women with karyotypically normal premature ovarian failure (POF). We measured BMD at the 1/3 distal radius (D-Rad(1/3); predominantly cortical bone) and at the ultradistal radius (UD-Rad; predominantly trabecular bone) by dual x-ray absorptiometry. Women with TS had lower cortical BMD compared with POF (D-Rad(1/3) Z-score = -1.5 +/- 0.8 for TS and 0.08 +/- 0.7 for POF; P < 0.0001). In contrast, the primarily trabecular UD-Rad BMD was normal in TS and not significantly different from POF (Z-score = -0.62 +/- 1.1 for TS and -0.34 +/- 1.0 for POF; P = 0.26). The difference in cortical BMD remained after adjustment for height, age of puberty, lifetime estrogen exposure, and serum 25-hydroxyvitamin D (P = 0.0013). Cortical BMD was independent of serum IGF-I and -II, PTH, and testosterone in TS. We conclude that there is a selective deficiency in forearm cortical bone in TS that appears independent of ovarian hormone exposure and is probably related to X-chromosome gene(s) haploinsufficiency.

Ultrasound arthroscopy of human knee cartilage and subchondral bone in vivo.

PubMed

Liukkonen, Jukka; Lehenkari, Petri; Hirvasniemi, Jukka; Joukainen, Antti; Virén, Tuomas; Saarakkala, Simo; Nieminen, Miika T; Jurvelin, Jukka S; Töyräs, Juha

2014-09-01

Arthroscopic ultrasound imaging enables quantitative evaluation of articular cartilage. However, the potential of this technique for evaluation of subchondral bone has not been investigated in vivo. In this study, we address this issue in clinical arthroscopy of the human knee (n = 11) by determining quantitative ultrasound (9 MHz) reflection and backscattering parameters for cartilage and subchondral bone. Furthermore, in each knee, seven anatomical sites were graded using the International Cartilage Repair Society (ICRS) system based on (i) conventional arthroscopy and (ii) ultrasound images acquired in arthroscopy with a miniature transducer. Ultrasound enabled visualization of articular cartilage and subchondral bone. ICRS grades based on ultrasound images were higher (p < 0.05) than those based on conventional arthroscopy. The higher ultrasound-based ICRS grades were expected as ultrasound reveals additional information on, for example, the relative depth of the lesion. In line with previous literature, ultrasound reflection and scattering in cartilage varied significantly (p < 0.05) along the ICRS scale. However, no significant correlation between ultrasound parameters and structure or density of subchondral bone could be demonstrated. To conclude, arthroscopic ultrasound imaging had a significant effect on clinical grading of cartilage, and it was found to provide quantitative information on cartilage. The lack of correlation between the ultrasound parameters and bone properties may be related to lesser bone change or excessive attenuation in overlying cartilage and insufficient power of the applied miniature transducer. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Effect of in vitro chondrogenic differentiation of autologous mesenchymal stem cells on cartilage and subchondral cancellous bone repair in osteoarthritis of temporomandibular joint.

PubMed

Chen, K; Man, C; Zhang, B; Hu, J; Zhu, S S

2013-02-01

This study investigated the effects of in vitro chondrogenic differentiated mesenchymal stem cells (MSCs) on cartilage and subchondral cancellous bone in temporomandibular joint osteoarthritis (TMJOA). Four weeks after induction of osteoarthritis (OA), the joints received hylartin solution, non-chondrogenic MSCs or in vitro chondrogenic differentiated MSCs. The changes in cartilage and subchondral cancellous bone were evaluated by histology, reverse transcription polymerase chain reaction and micro-computed tomography (CT). Implanted cells were tracked using Adeno-LacZ labelling. The differentiated MSC-treated group had better histology than the MSC-treated group at 4 and 12 weeks, but no difference at 24 weeks. Increased mRNA expression of collegan II, aggeran, Sox9 and decreased matrix metalloproteinase 13 (MMP13) were observed in differentiated MSC-treated groups compared to the undifferentiated MSC-treated group at 4 weeks. The differentiated MSC-treated group had decreased bone volume fraction, trabecular thickness and bone surface density, and increased trabecular spacing in the subchondral cancellous bone than the undifferentiated MSC-treated group. Transplanted cells were observed at cartilage, subchondral bone, and the synovial membrane lining at 4 weeks. Intra-articular injection of MSCs could delay the progression of TMJOA, and in vitro chondrogenic induction of MSCs could enhance the therapeutic effects. This provides new insights into the role of MSCs in cell-based therapies for TMJOA. Copyright © 2012 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

A study of the progression of damage in an axially loaded Branta leucopsis femur using X-ray computed tomography and digital image correlation.

PubMed

Mustansar, Zartasha; McDonald, Samuel A; Sellers, William Irvin; Manning, Phillip Lars; Lowe, Tristan; Withers, Philip J; Margetts, Lee

2017-01-01

This paper uses X-ray computed tomography to track the mechanical response of a vertebrate (Barnacle goose) long bone subjected to an axial compressive load, which is increased gradually until failure. A loading rig was mounted in an X-ray computed tomography system so that a time-lapse sequence of three-dimensional (3D) images of the bone's internal (cancellous or trabecular) structure could be recorded during loading. Five distinct types of deformation mechanism were observed in the cancellous part of the bone. These were (i) cracking, (ii) thinning (iii) tearing of cell walls and struts, (iv) notch formation, (v) necking and (vi) buckling. The results highlight that bone experiences brittle (notch formation and cracking), ductile (thinning, tearing and necking) and elastic (buckling) modes of deformation. Progressive deformation, leading to cracking was studied in detail using digital image correlation. The resulting strain maps were consistent with mechanisms occurring at a finer-length scale. This paper is the first to capture time-lapse 3D images of a whole long bone subject to loading until failure. The results serve as a unique reference for researchers interested in how bone responds to loading. For those using computer modelling, the study not only provides qualitative information for verification and validation of their simulations but also highlights that constitutive models for bone need to take into account a number of different deformation mechanisms.

Rapid detection of food pathogens using RNA aptamers-immobilized slide.

PubMed

Maeng, Jin-Soo; Kim, Namsoo; Kim, Chong-Tai; Han, Seung Ryul; Lee, Young Ju; Lee, Seong-Wook; Lee, Myung-Hyun; Cho, Yong-Jin

2012-07-01

The purpose of this study was to develop a simple and rapid detection system for foodborne bacteria, which consisted of an optical microscope and its slide chip with artificial antibodies, or RNA aptamers. From an RNA pool, three each RNA aptamers were built by the method of SELEX (systematic evolution of ligands by exponential enrichment) for components of cell wall, LPS (lipopolysaccharide) from E. coli O157:H7, teichoic acid from Staphylococcus aureus and a cell membrane protein of OmpC from Salmonella typhimurium, respectively. These aptamers were hybridized with thiol-conjugated 16 dT-linker molecules in order to be immobilized on silver surface which was, in advance, fabricated on glass slide, using a spin-coating method. To confirm that each aptamers retained its specific binding activities to their antigenic live bacteria, microscopic view of bound cells immobilized on silver film were observed. Furthermore, we observed the fluorescence-emitting bacteria-aptamer complex immobilized on silver film after adding RNA aptamers hybridized with fluorophore, FAM-conjugated 16 dT-linker molecules. As a result, the RNA aptamers-immobilized slide system developed in this study was a useful new tool to rapidly monitor individual food pathogens.

Colistin resistance associated with outer membrane protein change in Klebsiella pneumoniae and Enterobacter asburiae.

PubMed

Kádár, Béla; Kocsis, Béla; Tóth, Ákos; Kristóf, Katalin; Felső, Péter; Kocsis, Béla; Böddi, Katalin; Szabó, Dóra

2017-06-01

In this study, outer membrane proteins (OMPs) of colistin-resistant Klebsiella pneumoniae and Enterobacter asburiae were analyzed. One colistin-susceptible and three colistin-resistant K. pneumoniae sequence type 258 strains as well as one colistin-susceptible E. asburiae and its colistin-heteroresistant counterpart strain were involved in the study. OMP analysis of each strain was performed by microchip method. Matrix-assisted laser desorption ionization time of flight/mass spectrometry (MALDI-TOF/MS) investigation was carried out after separation of OMPs by two-dimensional gel electrophoresis and in-gel digestion. The MALDI-TOF/MS analysis of OMPs in the colistin-susceptible K. pneumoniae found 16 kDa proteins belonging to the LysM domain/BON superfamily, as well as DNA starvation proteins, whereas OmpX and OmpW were detected in the colistin-resistant counterpart strains. OmpC and OmpW were detected in the colistin-susceptible E. asburiae, whereas OmpA and OmpX were identified in the colistin-resistant counterpart. This study demonstrated that OMP differences were between colistin-susceptible and -resistant counterpart strains. The altered Gram-negative cell wall may contribute to acquired colistin resistance in Enterobacteriaceae.

Pathologic Changes of the Peripheral Vestibular System Secondary to Chronic Otitis Media.

PubMed

da Costa Monsanto, Rafael; Erdil, Mehmet; Pauna, Henrique F; Kwon, Geeyoun; Schachern, Patricia A; Tsuprun, Vladimir; Paparella, Michael M; Cureoglu, Sebahattin

2016-09-01

To evaluate the histopathologic changes of dark, transitional, and hair cells of the vestibular system in human temporal bones from patients with chronic otitis media. Comparative human temporal bone study. Otopathology laboratory. To compare the density of vestibular dark, transitional, and hair cells in temporal bones with and without chronic otitis media, we used differential interference contrast microscopy. In the chronic otitis media group (as compared with the age-matched control group), the density of type I and type II hair cells was significantly decreased in the lateral semicircular canal, saccule, and utricle (P < .05). The density of type I cells was also significantly decreased in the chronic otitis media group in the posterior semicircular canal (P = .005), but that of type II cells was not (P = .168). The mean number of dark cells was significantly decreased in the chronic otitis media group in the lateral semicircular canal (P = .014) and in the posterior semicircular canal (P = .002). We observed no statistically significant difference in the density of transitional cells between the 2 groups (P > .1). The findings of our study suggest that the decrease in the number of vestibular sensory cells and dark cells could be the cause of the clinical symptoms of imbalance of some patients with chronic otitis media. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

Resolution of bone marrow fibrosis in a patient receiving JAK1/JAK2 inhibitor treatment with ruxolitinib.

PubMed

Wilkins, Bridget S; Radia, Deepti; Woodley, Claire; Farhi, Sarah El; Keohane, Clodagh; Harrison, Claire N

2013-12-01

Ruxolitinib, a JAK1/JAK2 inhibitor, is currently the only pharmacological agent approved for the treatment of myelofibrosis. Approval was based on findings from two phase 3 trials comparing ruxolitinib with placebo (COMFORT-I) and with best available therapy (COMFORT-II) for the treatment of primary or secondary myelofibrosis. In those pivotal trials, ruxolitinib rapidly improved splenomegaly, disease-related symptoms, and quality of life and prolonged survival compared with both placebo and conventional treatments. However, for reasons that are currently unclear, there were only modest histomorphological changes in the bone marrow, and only a subset of patients had significant reductions in JAK2 V617F clonal burden. Here we describe a patient with post-polycythemia vera myelofibrosis who received ruxolitinib at our institution (Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom) as part of the COMFORT-II study. While on treatment, the patient had dramatic improvements in splenomegaly and symptoms shortly after starting ruxolitinib. With longer treatment, the patient had marked reductions in JAK2 V617F allele burden, and fibrosis of the bone marrow resolved after approximately 3 years of ruxolitinib treatment. To our knowledge, this is the first detailed case report of resolution of fibrosis with a JAK1/JAK2 inhibitor. ClinicalTrials.gov Identifier: NCT00934544.

Differences in the stress distribution in the distal femur between patellofemoral joint replacement and total knee replacement: a finite element study

PubMed Central

2012-01-01

Background Patellofemoral joint replacement is a successful treatment option for isolated patellofemoral osteoarthritis. However, results of later conversion to total knee replacement may be compromised by periprosthetic bone loss. Previous clinical studies have demonstrated a decrease in distal femoral bone mineral density after patellofemoral joint replacement. It is unclear whether this is due to periprosthetic stress shielding. The main objective of the current study was to evaluate the stress shielding effect of prosthetic replacement with 2 different patellofemoral prosthetic designs and with a total knee prosthesis. Methods We developed a finite element model of an intact patellofemoral joint, and finite element models of patellofemoral joint replacement with a Journey PFJ prosthesis, a Richards II prosthesis, and a Genesis II total knee prosthesis. For each of these 4 finite element models, the average Von Mises stress in 2 clinically relevant regions of interest were evaluated during a simulated squatting movement until 120 degrees of flexion. Results During deep knee flexion, in the anterior region of interest, the average Von Mises stress with the Journey PFJ design was comparable to the physiological knee, while reduced by almost 25% for both the Richards II design and the Genesis II total knee joint replacement design. The average Von Mises stress in the supracondylar region of interest was similar for both patellofemoral prosthetic designs and the physiological model, with slightly lower stress for the Genesis II design. Conclusions Patellofemoral joint replacement results in periprosthetic stress-shielding, although to a smaller degree than in total knee replacement. Specific patellofemoral prosthetic design properties may result in differences in femoral stress shielding. PMID:22704638

Neurologic aspects of microcephalic osteodysplastic primordial dwarfism type II.

PubMed

Galasso, Cinzia; Lo-Castro, Adriana; Lalli, Cristina; Cerminara, Caterina; Curatolo, Paolo

2008-06-01

Microcephalic osteodysplastic primordial dwarfism type II is a specific disorder characterized by severe intrauterine and postnatal growth retardation, acquired microcephaly, cerebrovascular abnormalities, progressive bone dysplasia, and a characteristic face. Whereas the diagnostic features of this syndrome are well-recognized, the neurologic aspects have not been clearly defined. We report on a detailed neurodevelopmental follow-up study of a new case of microcephalic osteodysplastic primordial dwarfism type II, followed from the first years of life to adolescence, and we discuss the neurocognitive features of our patient. We also review the neurologic aspects of this disorder compared with syndromes with overlapping phenotypes, such as microcephalic osteodysplastic primordial dwarfism types I and III and Seckel syndrome.

21 CFR 862.1295 - Folic acid test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... treatment of megaloblastic anemia, which is characterized by the presence of megaloblasts (an abnormal red blood cell series) in the bone marrow. (b) Classification. Class II. [52 FR 16122, May 1, 1987; 53 FR....1295 Folic acid test system. (a) Identification. A folic acid test system is a device intended to...

TGF-β/BMP signaling and other molecular events: regulation of osteoblastogenesis and bone formation

PubMed Central

Rahman, Md Shaifur; Akhtar, Naznin; Jamil, Hossen Mohammad; Banik, Rajat Suvra; Asaduzzaman, Sikder M

2015-01-01

Transforming growth factor-beta (TGF-β)/bone morphogenetic protein (BMP) plays a fundamental role in the regulation of bone organogenesis through the activation of receptor serine/threonine kinases. Perturbations of TGF-β/BMP activity are almost invariably linked to a wide variety of clinical outcomes, i.e., skeletal, extra skeletal anomalies, autoimmune, cancer, and cardiovascular diseases. Phosphorylation of TGF-β (I/II) or BMP receptors activates intracellular downstream Smads, the transducer of TGF-β/BMP signals. This signaling is modulated by various factors and pathways, including transcription factor Runx2. The signaling network in skeletal development and bone formation is overwhelmingly complex and highly time and space specific. Additive, positive, negative, or synergistic effects are observed when TGF-β/BMP interacts with the pathways of MAPK, Wnt, Hedgehog (Hh), Notch, Akt/mTOR, and miRNA to regulate the effects of BMP-induced signaling in bone dynamics. Accumulating evidence indicates that Runx2 is the key integrator, whereas Hh is a possible modulator, miRNAs are regulators, and β-catenin is a mediator/regulator within the extensive intracellular network. This review focuses on the activation of BMP signaling and interaction with other regulatory components and pathways highlighting the molecular mechanisms regarding TGF-β/BMP function and regulation that could allow understanding the complexity of bone tissue dynamics. PMID:26273537

Influence of ferutinin on bone metabolism in ovariectomized rats. II: Role in recovering osteoporosis

PubMed Central

Ferretti, Marzia; Bertoni, Laura; Cavani, Francesco; Zavatti, Manuela; Resca, Elisa; Carnevale, Gianluca; Benelli, Augusta; Zanoli, Paola; Palumbo, Carla

2010-01-01

The aim of the present investigation, which represents an extension of a previous study, was to investigate the effect of ferutinin in recovering severe osteoporosis due to estrogen deficiency after rat ovariectomy and to compare phytoestrogen effects with those of estrogens commonly used in hormone replacement therapy (HRT) by women with postmenopausal osteoporosis. The animal model used was the Sprague–Dawley ovariectomized rat. Ferutinin was orally administered (2 mg kg−1 per day) for 30 or 60 days starting from 2 months after ovariectomy (i.e. when osteoporosis was clearly evident) and its effects were compared with those of estradiol benzoate (1.5 μg per rat twice a week, subcutaneously injected) vs. vehicle-treated ovariectomized (OVX) and sham-operated (SHAM) rats. Histomorphometric analyses were performed on trabecular bone of lumbar vertebrae (4th and 5th) and distal femoral epiphysis, as well as on cortical bone of femoral diaphysis. Bone histomorphometric analyses showed that ferutinin seems to display the same effects on bone mass recorded with estradiol benzoate, thus suggesting that it could enhance the recovery of bone loss due to severe estrogen deficiency in OVX rats. On this basis, the authors propose listing ferutinin among the substances representing a potential alternative for the treatment of postmenopausal osteoporosis, which occurs as a result of estrogen deficiency. PMID:20492429

A new Fe-Mn-Si alloplastic biomaterial as bone grafting material: In vivo study

NASA Astrophysics Data System (ADS)

Fântânariu, Mircea; Trincă, Lucia Carmen; Solcan, Carmen; Trofin, Alina; Strungaru, Ştefan; Şindilar, Eusebiu Viorel; Plăvan, Gabriel; Stanciu, Sergiu

2015-10-01

Designing substrates having suitable mechanical properties and targeted degradation behavior is the key's development of bio-materials for medical application. In orthopedics, graft material may be used to fill bony defects or to promote bone formation in osseous defects created by trauma or surgical intervention. Incorporation of Si may increase the bioactivity of implant locally, both by enhancing interactions at the graft-host interface and by having a potential endocrine like effect on osteoblasts. A Fe-Mn-Si alloy was obtained as alloplastic graft materials for bone implants that need long recovery time period. The surface morphology of the resulted specimens was investigated using scanning electrons microscopy (VegaTescan LMH II, SE detector, 30 kV), X-ray diffractions (X'Pert equipment) or X-ray dispersive energy analyze (Bruker EDS equipment). This study objective was to evaluate in vivo the mechanisms of degradation and the effects of its implantation over the main metabolic organs. Biochemical, histological, plain X radiography and computed tomography investigations showed good compatibility of the subcutaneous implants in the rat organism. The implantation of the Fe-Mn-Si alloy, in critical size bone (tibiae) defect rat model, did not induced adverse biological reactions and provided temporary mechanical support to the affected bone area. The biodegradation products were hydroxides layers which adhered to the substrate surface. Fe-Mn-Si alloy assured the mechanical integrity in rat tibiae defects during bone regeneration.

[MRI characteristic of proximal femur bone marrow edema syndrome].

PubMed

Wu, Xi-Yuan

2014-07-01

To study the MRI features of proximal femur bone marrow edema syndrome for further improve the understanding of the disease. MRI imaging of 10 patients with proximal femur bone marrow edema syndrome was retrospectively reviewed,including 6 males and 4 females with an average age of 41.5 years old ranging from 36 to 57. The courses of diseases ranged from 1 week to 3 months. Among them, 9 cases had clinical manifestations of sudden hip pain, 7 cases had limited ability of walking and hip movement;all patients had no obvious injury history, non of the female patients was pregnant. All patients were followed up from 3 to 12 months, the following-up were topped after MRI when the symptoms disappeared for 3 months. The MRI demonstrated diffuse bone marrow edema involving the femoral head, neck and the inter-trochanteric region, 13 hips of 10 patients with bone marrow edema included 6 cases in grade 1, 5 cases in grade 2,2 cases in grade 3; 9 hips with hip hydrarthrosis included 6 hips in grade I ,1 hip in grade II, 2 hips in grade III. After treatment for 3 to 12 months the hip symptoms of the patients disappeared and MRI images were normal. MRI is useful in defining the location and extent of proximal femur bone marrow edema syndrome.

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

PubMed

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

2013-07-01

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

A Primary Investigation on Serum CTX-II Changes in Patients Infected with Brucellosis in Qinghai Plateau, China.

PubMed

Zhao, Zhi Jun; Li, Qiang; Zhou, Xin; Ma, Li; Xu, Li Qing; Yang, Pei Zhen; Meng, Xian Ya; Yu, Hui Zhen; Xu, Xiao Qing; Cao, Jian Ying

2016-03-01

Brucellosis is one of the most widespread zoonotic diseases, with the most frequent complication being osteoarticular changes. The aim of this study was to assess the changes of C-terminal telopeptide of type II collagen (CTX-II) in patients infected with brucellosis. A total of 84 brucellosis patients and 43 volunteers were selected and divided into brucellosis vs. control groups. Serum samples were subjected to serological tests for brucellosis, and CTX-II levels in all samples were measured simultaneously with ELISA. The results showed that serum CTX-II levels in human brucellosis were higher than those of healthy controls, without a statistically significant difference, but serum CTX-II levels in male patients were significantly higher than those of female patients (P<0.05). This finding could indicate the biological changes in the cartilage and bone in human brucellosis. Copyright © 2016 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

A Phase II Trial on the Effect of Low-Dose versus High-Dose Vitamin D Supplementation on Bone Mass in Adults with Neurofibromatosis 1 (NF1)

DTIC Science & Technology

2013-10-01

MD, PhD CONTRACTING ORGANIZATION: University of Utah REPORT DATE : October 2013 TYPE OF REPORT: Annual PREPARED FOR: U.S...of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE ...October 2013 2. REPORT TYPE Annual 3. DATES COVERED 15 September 2012-14 September 2013 4. TITLE AND SUBTITLE A Phase II Trial on the Effect of

Healing of a mechano-responsive material

NASA Astrophysics Data System (ADS)

Vetter, A.; Sander, O.; Duda, G. N.; Weinkamer, R.

2013-12-01

While contribution of physics to model fracture of materials is significant, the “reversed” process of healing is hardly investigated. Inspired by fracture healing that occurs as a self-repair process in nature, e.g. in bone, we computationally study the conditions under which a material can repair itself. In our model the material around a fracture is assumed mechano-responsive: it processes the information of i) local stiffness and ii) local strain and responds by local stiffening. Depending on how information i) and ii) is processed, healing evolves via fundamentally different paths.

Percutaneous internal fixation of proximal fifth metatarsal jones fractures (Zones II and III) with Charlotte Carolina screw and bone marrow aspirate concentrate: an outcome study in athletes.

PubMed

Murawski, Christopher D; Kennedy, John G

2011-06-01

Internal fixation is a popular first-line treatment method for proximal fifth metatarsal Jones fractures in athletes; however, nonunions and screw breakage can occur, in part because of nonspecific fixation hardware and poor blood supply. To report the results from 26 patients who underwent percutaneous internal fixation with a specialized screw system of a proximal fifth metatarsal Jones fracture (zones II and III) and bone marrow aspirate concentrate. Case series; Level of evidence, 4. Percutaneous internal fixation for a proximal fifth metatarsal Jones fracture (zones II and III) was performed on 26 athletic patients (mean age, 27.47 years; range, 18-47). All patients were competing at some level of sport and were assessed preoperatively and postoperatively using the Foot and Ankle Outcome Score and SF-12 outcome scores. The mean follow-up time was 20.62 months (range, 12-28). Of the 26 fractures, 17 were traditional zone II Jones fractures, and the remaining 9 were zone III proximal diaphyseal fractures. The mean Foot and Ankle Outcome Score significantly increased, from 51.15 points preoperatively (range, 14-69) to 90.91 at final follow-up (range, 71-100; P < .01). The mean physical component of the SF-12 score significantly improved, from 25.69 points preoperatively (range, 6-39) to 54.62 at final follow-up (range, 32-62; P < .01). The mean mental component of the SF-12 score also significantly improved, from 28.20 points preoperatively (range, 14-45) to 58.41 at final follow-up (range, 36-67; P < .01). The mean time to fracture healing on standard radiographs was 5 weeks after surgery (range, 4-24). Two patients did not return to their previous levels of sporting activity. One patient experienced a delayed union, and 1 healed but later refractured. Percutaneous internal fixation of proximal fifth metatarsal Jones fractures, with a Charlotte Carolina screw and bone marrow aspirate concentrate, provides more predictable results while permitting athletes a return to sport at their previous levels of competition, with few complications.

Cross-sectional geometry of Pecos Pueblo femora and tibiae--a biomechanical investigation: II. Sex, age, side differences.

PubMed

Ruff, C B; Hayes, W C

1983-03-01

Intra-populational variation in cross-sectional geometric properties of the femur and tibia are investigated in the Pecos Pueblo skeletal sample. Sex differences in geometric parameters suggest that male lower limb bones are more adapted for A-P bending, females for M-L bending. Proposed explanations for this finding include sexual dimorphism in pelvic structure and culturally prescribed sex-related activities at Pecos. With aging, both males and females undergo endosteal resorption and cortical thinning, greater among females. Both sexes also demonstrate an increase with age in subperiosteal area and second moments of area, supporting results reported in some studies of modern population samples. Sex and site-specific remodeling of the femur and tibia with aging also occur. These localized remodeling changes appear to selectively conserve more compact cortical bone in areas of high mechanical stress. Side differences in cross-sectional geometric properties indicate that left lower limb bones are generally larger than right lower limb bones, with asymmetry greater among females. In particular, left femora and tibiae are relatively stronger in A-P bending, again more so in females.

Acute myelogenous leukemia cells with the MLL-ELL translocation convert morphologically and functionally into adherent myofibroblasts

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

Tashiro, Haruko; Mizutani-Noguchi, Mitsuho; Shirasaki, Ryosuke

2010-01-01

Bone marrow-myofibroblasts, a major component of bone marrow-stroma, are reported to originate from hematopoietic stem cells. We show in this paper that non-adherent leukemia blasts can change into myofibroblasts. When myeloblasts from two cases of acute myelogenous leukemia with a fusion product comprising mixed lineage leukemia and RNA polymerase II elongation factor, were cultured long term, their morphology changed to that of myofibroblasts with similar molecular characteristics to the parental myeloblasts. The original leukemia blasts, when cultured on the leukemia blast-derived myofibroblasts, grew extensively. Leukemia blasts can create their own microenvironment for proliferation.

Influence of Drilling Speed on Stability of Tapered Dental Implants: An Ex Vivo Experimental Study.

PubMed

Almeida, Karen P; Delgado-Ruiz, Rafael; Carneiro, Leandro G; Leiva, Alberto Bordonaba; Calvo-Guirado, Jose Luis; Gómez-Moreno, Gerardo; Malmström, Hans; Romanos, Georgios E

2016-01-01

The aim of this study was to evaluate whether the drilling speed used during implant site preparation influences primary stability. Eighty tapered designed implants (3.8 × 10 mm) were inserted following osteotomies created in solid rigid polyurethane foam (simulating bone type II) and cellular rigid polyurethane foam (simulating bone type IV). Half were prepared using drilling speeds of 800 rpm (low speed), and the other half were prepared using speeds of 1,500 rpm (high speed). Following insertion, implant primary stability was measured using Periotest and Osstell (resonance frequency analysis [RFA]) devices. Two-way analysis of variance (ANOVA) used for this study found that the drilling speed used to create the osteotomies appeared to have no significant impact on primary stability. The bone quality and not the osteotomy drilling speed seems to influence the implant primary stability.

TOMOGRAPHIC MORPHOLOGICAL STUDY OF THE CRANIUM AND ITS CORRELATION WITH CRANIAL HALO USE IN ADULTS

PubMed Central

ALMEIDA, TIAGO FERREIRA DE; CHARAFEDDINE, HOMAR TOLEDO; ARAÚJO, FERNANDO FLORES DE; CRISTANTE, ALEXANDRE FOGAÇA; MARCON, RAPHAEL MARTUS; LETAIF, OLAVO BIRAGHI

2017-01-01

ABSTRACT Objective: To evaluate using tomographic study the thickness of the cranial board at the insertions points of the cranial halo pins in adults Methods: This is a retrospective, cross-sectional, descriptive analysis of Computed Tomography (CT) scans of adult patients' crania. The study included adults between 20 and 50 years without cranial abnormalities. We excluded any exam with cranial abnormalities Results: We analyzed 50 CT scans, including 27 men and 23 women, at the original insertion points and alternative points (1 and 2 cm above the frontal and parietal bones). The average values were 7.4333 mm in the frontal bone and 6.0290 mm in the parietal bone Conclusion: There was no statistically significant difference between the classical and alternative points, making room for alternative fixings and safer introduction of the pins, if necessary.Level of Evidence II, Retrospective Study. PMID:28642643

Opportunities for exercise during pullet rearing, Part II: Long-term effects on bone characteristics of adult laying hens at the end-of-lay.

PubMed

Casey-Trott, T M; Korver, D R; Guerin, M T; Sandilands, V; Torrey, S; Widowski, T M

2017-08-01

Osteoporosis in laying hens has been a production and welfare concern for several decades. The objective of this study was to determine whether differing opportunities for exercise during pullet rearing influences long-term bone quality characteristics in end-of-lay hens. A secondary objective was to assess whether differing opportunities for exercise in adult housing systems alters bone quality characteristics in end-of-lay hens. Four flock replicates of 588 Lohmann Selected Leghorn-Lite pullets were reared in either conventional cages (Conv) or an aviary rearing system (Avi) and placed into conventional cages (CC), 30-bird furnished cages (FC-S), or 60-bird furnished cages (FC-L) for adult housing. Wing and leg bones were collected at the end-of-lay to quantify bone composition and strength using quantitative computed tomography and bone breaking strength (BBS). At the end-of-lay, Avi hens had greater total and cortical cross-sectional area (P < 0.05) for the radius and tibia, greater total bone mineral content of the radius (P < 0.001), and greater tibial cortical bone mineral content (P = 0.029) than the Conv hens; however, total bone mineral density of the radius (P < 0.001) and cortical bone mineral density of the radius and tibia (P < 0.001) were greater in the Conv hens. Hens in the FC-L had greater total bone mineral density for the radius and tibia (P < 0.05) and greater trabecular bone mineral density for the radius (P = 0.027), compared to hens in the FC-S and CC. Total bone mineral content of the tibia (P = 0.030) and cortical bone mineral content of the radius (P = 0.030) and tibia (P = 0.013) were greater in the FC-L compared to the CC. The humerus of Conv hens had greater BBS than the Avi hens (P < 0.001), and the tibiae of FC-L and FC-S hens had greater BBS than CC hens (P = 0.006). Increased opportunities for exercise offered by the aviary rearing system provided improved bone quality characteristics lasting through to the end-of-lay. © The Author 2017. Published by Oxford University Press on behalf of Poultry Science Association.

Relationships between biomarkers of cartilage, bone, synovial metabolism and knee pain provide insights into the origins of pain in early knee osteoarthritis.

PubMed

Ishijima, Muneaki; Watari, Taiji; Naito, Kiyohito; Kaneko, Haruka; Futami, Ippei; Yoshimura-Ishida, Kaori; Tomonaga, Akihito; Yamaguchi, Hideyo; Yamamoto, Tetsuro; Nagaoka, Isao; Kurosawa, Hisashi; Poole, Robin A; Kaneko, Kazuo

2011-02-14

We tested the hypothesis that there exist relationships between the onset of early stage radiographically defined knee osteoarthritis (OA), pain and changes in biomarkers of joint metabolism. Using Kellgren-Lawrence (K/L) grading early radiographic knee OA (K/L 2) was detected in 16 of 46 patients. These grades (K/L 1 is no OA and K/L 2 is early OA) were divided into two groups according to the presence or absence of persistent knee pain. Sera (s) and urines (u) were analysed with biomarkers for cartilage collagen cleavage (sC2C and uCTX-II) and synthesis (sCPII), bone resorption (uNTx) and synovitis (hyaluronic acid: sHA). sCPII decreased and sC2C/sCPII, uCTX-II/sCPII and sHA increased with onset of OA (K/L 2 versus K/L 1) irrespective of joint pain. In contrast, sC2C and uCTX-II remained unchanged in early OA patients. Of the patients with K/L grades 1 and 2 sC2C, sCPII, sHA, uNTX and uCTX-II were all significantly increased in patients with knee pain independent of grade. Among the K/L grade 2 subjects, only uCTX-II and uCTX-II/sCPII were increased in those with knee pain. In grade 1 patients both sC2C and sCPII were increased in those with knee pain. No such grade specific changes were seen for the other biomarkers including sHA. These results suggest that changes in cartilage matrix turnover detected by molecular biomarkers may reflect early changes in cartilage structure that account directly or indirectly for knee pain. Also K/L grade 1 patients with knee pain exhibit biomarker features of early OA.

Commensal Microbiota Enhance Both Osteoclast and Osteoblast Activities.

PubMed

Uchida, Yoko; Irie, Koichiro; Fukuhara, Daiki; Kataoka, Kota; Hattori, Takako; Ono, Mitsuaki; Ekuni, Daisuke; Kubota, Satoshi; Morita, Manabu

2018-06-23

Recent studies suggest that the commensal microbiota affects not only host energy metabolism and development of immunity but also bone remodeling by positive regulation of osteoclast activity. However, the mechanism of regulation of bone cells by the commensal microbiota has not been elucidated. In this study, 8-week-old specific pathogen-free (SPF) and germ-free (GF) mice were compared in terms of alveolar bones and primary osteoblasts isolated from calvarias. Micro-CT analysis showed that SPF mice had larger body size associated with lower bone mineral density and bone volume fraction in alveolar bones compared with GF mice. Greater numbers of osteoclasts in alveolar bone and higher serum levels of tartrate-resistant acid phosphatase 5b were observed in SPF mice. Tissue extracts from SPF alveolar bone showed higher levels of cathepsin K, indicating higher osteoclast activity. SPF alveolar extracts also showed elevated levels of γ-carboxylated glutamic acid⁻osteocalcin as a marker of mature osteoblasts compared with GF mice. Polymerase chain reaction (PCR) array analysis of RNA directly isolated from alveolar bone showed that in SPF mice, expression of mRNA of osteocalcin , which also acts as an inhibitor of bone mineralization, was strongly enhanced compared with GF mice. Cultured calvarial osteoblasts from SPF mice showed reduced mineralization but significantly enhanced expression of mRNAs of osteocalcin, alkaline phosphatase, insulin-like growth factor-I/II , and decreased ratio of osteoprotegerin/receptor activator of nuclear factor-kappa B ligand compared with GF mice. Furthermore, PCR array analyses of transcription factors in cultured calvarial osteoblasts showed strongly upregulated expression of Forkhead box g1 . In contrast, Gata-binding protein 3 was strongly downregulated in SPF osteoblasts. These results suggest that the commensal microbiota prevents excessive mineralization possibly by stimulating osteocalcin expression in osteoblasts, and enhances both osteoblast and osteoclast activity by regulating specific transcription factors.

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

PubMed

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

2006-08-05

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

High fluoride and low calcium levels in drinking water is associated with low bone mass, reduced bone quality and fragility fractures in sheep.

PubMed

Simon, M J K; Beil, F T; Rüther, W; Busse, B; Koehne, T; Steiner, M; Pogoda, P; Ignatius, A; Amling, M; Oheim, R

2014-07-01

Chronic environmental fluoride exposure under calcium stress causes fragility fractures due to osteoporosis and bone quality deterioration, at least in sheep. Proof of skeletal fluorosis, presenting without increased bone density, calls for a review of fracture incidence in areas with fluoridated groundwater, including an analysis of patients with low bone mass. Understanding the skeletal effects of environmental fluoride exposure especially under calcium stress remains an unmet need of critical importance. Therefore, we studied the skeletal phenotype of sheep chronically exposed to highly fluoridated water in the Kalahari Desert, where livestock is known to present with fragility fractures. Dorper ewes from two flocks in Namibia were studied. Chemical analyses of water, blood and urine were executed for both cohorts. Skeletal phenotyping comprised micro-computer tomography (μCT), histological, histomorphometric, biomechanical, quantitative backscattered electron imaging (qBEI) and energy-dispersive X-ray (EDX) analysis. Analysis was performed in direct comparison with undecalcified human iliac crest bone biopsies of patients with fluoride-induced osteopathy. The fluoride content of water, blood and urine was significantly elevated in the Kalahari group compared to the control. Surprisingly, a significant decrease in both cortical and trabecular bones was found in sheep chronically exposed to fluoride. Furthermore, osteoid parameters and the degree and heterogeneity of mineralization were increased. The latter findings are reminiscent of those found in osteoporotic patients with treatment-induced fluorosis. Mechanical testing revealed a significant decrease in the bending strength, concurrent with the clinical observation of fragility fractures in sheep within an area of environmental fluoride exposure. Our data suggest that fluoride exposure with concomitant calcium deficit (i) may aggravate bone loss via reductions in mineralized trabecular and cortical bone mass and (ii) can cause fragility fractures and (iii) that the prevalence of skeletal fluorosis especially due to groundwater exposure should be reviewed in many areas of the world as low bone mass alone does not exclude fluorosis.

Hyperlipidemia affects multiscale structure and strength of murine femur.

PubMed

Ascenzi, Maria-Grazia; Lutz, Andre; Du, Xia; Klimecky, Laureen; Kawas, Neal; Hourany, Talia; Jahng, Joelle; Chin, Jesse; Tintut, Yin; Nackenhors, Udo; Keyak, Joyce

2014-07-18

To improve bone strength prediction beyond limitations of assessment founded solely on the bone mineral component, we investigated the effect of hyperlipidemia, present in more than 40% of osteoporotic patients, on multiscale structure of murine bone. Our overarching purpose is to estimate bone strength accurately, to facilitate mitigating fracture morbidity and mortality in patients. Because (i) orientation of collagen type I affects, independently of degree of mineralization, cortical bone׳s micro-structural strength; and, (ii) hyperlipidemia affects collagen orientation and μCT volumetric tissue mineral density (vTMD) in murine cortical bone, we have constructed the first multiscale finite element (mFE), mouse-specific femoral model to study the effect of collagen orientation and vTMD on strength in Ldlr(-/-), a mouse model of hyperlipidemia, and its control wild type, on either high fat diet or normal diet. Each µCT scan-based mFE model included either element-specific elastic orthotropic properties calculated from collagen orientation and vTMD (collagen-density model) by experimentally validated formulation, or usual element-specific elastic isotropic material properties dependent on vTMD-only (density-only model). We found that collagen orientation, assessed by circularly polarized light and confocal microscopies, and vTMD, differed among groups and that microindentation results strongly correlate with elastic modulus of collagen-density models (r(2)=0.85, p=10(-5)). Collagen-density models yielded (1) larger strains, and therefore lower strength, in simulations of 3-point bending and physiological loading; and (2) higher correlation between mFE-predicted strength and 3-point bending experimental strength, than density-only models. This novel method supports ongoing translational research to achieve the as yet elusive goal of accurate bone strength prediction. Copyright © 2014 Elsevier Ltd. All rights reserved.

Denosumab treatment of prostate cancer with bone metastases and increased urine N-telopeptide levels after therapy with intravenous bisphosphonates: results of a randomized phase II trial.

PubMed

Fizazi, Karim; Bosserman, Linda; Gao, Guozhi; Skacel, Tomas; Markus, Richard

2009-08-01

Patients with bone metastases have high rates of RANKL driven bone resorption and an increased risk of skeletal morbidity. Osteoclast mediated bone resorption can be assessed by measuring urine N-telopeptide and can be inhibited by denosumab, a fully human antibody against RANKL. Eligible patients (111) had bone metastases from prostate cancer, other solid tumors or multiple myeloma, 1 or more bone lesions and urine N-telopeptide greater than 50 nM bone collagen equivalents per mM creatinine (urine N-telopeptide greater than 50) despite the use of intravenous bisphosphonates. Patients were stratified by cancer type and screening urine N-telopeptide, and randomized to continue intravenous bisphosphonates every 4 weeks or receive 180 mg subcutaneous denosumab every 4 weeks or 180 mg every 12 weeks. The primary end point was the proportion of patients with urine N-telopeptide less than 50 at week 13. We report the efficacy results for the subset of patients with prostate cancer. Patients with prostate cancer represented 45% (50 of 111) of the study population. At week 13, 22 of 32 (69%) patients in the denosumab arms had urine N-telopeptide less than 50 vs 3 of 16 (19%) in the intravenous bisphosphonates cohort. At week 25, 22 of 32 (69%) denosumab treated patients continued to have urine N-telopeptide less than 50 vs 5 of 16 (31%) treated with intravenous bisphosphonates. Grade 4, asymptomatic, reversible hypophosphatemia, possibly related to denosumab, was reported in 1 patient. In patients with prostate cancer related bone metastases and increased urine N-telopeptide despite intravenous bisphosphonate treatment, denosumab normalized urine N-telopeptide levels more frequently than ongoing intravenous bisphosphonates.

Bone Morphogenetic Protein-7 Enhances Degradation of Osteoinductive Bioceramic Implants in an Ectopic Model

PubMed Central

Klünter, Tim; Schulz, Peter; Deisinger, Ulrike; Diez, Claudius; Waiss, Waltraud; Kirschneck, Christian; Reichert, Torsten E.; Detsch, Rainer

2017-01-01

Background: The aim of the present study was to evaluate the degradation pattern of highly porous bioceramics as well as the bone formation in presence of bone morphogenetic protein 7 (BMP-7) in an ectopic site. Methods: Novel calcium phosphate ceramic cylinders sintered at 1,300°C with a total porosity of 92–94 vol%, 45 pores per inch, and sized 15 mm (Ø) × 5 mm were grafted on the musculus latissimus dorsi bilaterally in 10 Göttingen minipigs: group I (n = 5): hydroxyapatite (HA) versus biphasic calcium phosphate (BCP), a mixture of HA and tricalcium phosphate (TCP) in a ratio of 60/40 wt%; group II (n = 5): TCP versus BCP. A test side was supplied in situ with 250 μg BMP-7. Fluorochrome bone labeling and computed tomography were performed in vivo. Specimens were evaluated 14 weeks after surgery by environmental scanning electron microscopy, fluorescence microscopy, tartrate-resistant acid phosphatase, and pentachrome staining. Results: Bone formation was enhanced in the presence of BMP-7 in all ceramics (P = 0.001). Small spots of newly formed bone were observed in all implants in the absence of BMP-7. Degradation of HA and BCP was enhanced in the presence of BMP-7 (P = 0.001). In those ceramics, osteoclasts were observed. TCP ceramics were almost completely degraded independently of the effect of BMP-7 after 14 weeks (P = 0.76), osteoclasts were not observed. Conclusions: BMP-7 enhanced bone formation and degradation of HA and BCP ceramics via osteoclast resorption. TCP degraded via dissolution. All ceramics were osteoinductive. Novel degradable HA and BCP ceramics in the presence of BMP-7 are promising bone substitutes in the growing individual. PMID:28740783

Losartan increases bone mass and accelerates chondrocyte hypertrophy in developing skeleton

PubMed Central

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

2015-01-01

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

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

PubMed

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

2015-05-01

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