|
| ||
|
|
||
Bone Remodelling (bone + remodelling)
Selected AbstractsBone remodelling following a lower leg fracture in the 11,000-year-old hunter-gatherer from Vado all' Arancio (Italy)INTERNATIONAL JOURNAL OF OSTEOARCHAEOLOGY, Issue 6 2002B. M. Holt Abstract The Upper Palaeolithic skeleton from Vado all'Arancio (Italy), dated to about 11,330 BP, exhibits a severe ankle fracture healed with residual deformation. Following recovery, this young hunter-gatherer continued to walk for an extended period of time, albeit in a mechanically altered manner. While right-left differences in external lower limb bone measurements are relatively low, biomechanical analysis of femur and tibia indicates unusually pronounced asymmetry in all cross-sectional measures of diaphyseal strength. Asymmetry results primarily from normal side endosteal hypertrophy, and not from hypotrophy of the injured limb, suggesting that this individual resumed active life following recovery. This pattern of asymmetry underscores the role of physical activity in maintaining bone mass. Copyright © 2002 John Wiley & Sons, Ltd. [source] Ovariectomy increases vascular calcification via the OPG/RANKL cytokine signalling pathwayEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 4 2008B. G. Choi ABSTRACT Background, Observational studies suggest a strong relationship between menopause and vascular calcification. Receptor activator of nuclear factor-,, ligand (RANKL) and osteoprotegerin (OPG) are critical regulators of bone remodelling and modulate vascular calcification. We assessed the hypothesis that ovariectomy increases vascular calcification via the OPG/RANKL axis. Materials and methods, Age-matched sexually mature rabbits were randomized to ovariectomy (OVX, n = 12) or sham procedure (SHAM, n = 12). One month post-procedure, atherosclerosis was induced by 15 months 0·2%-cholesterol diet and endothelial balloon denudations (at months 1 and 3). Aortic atherosclerosis was assessed in vivo by magnetic resonance imaging (MRI) at months 9 and 15. At sacrifice, aortas were harvested for ex vivo microcomputed tomography (µCT) and molecular analysis of the vascular tissue. Results, Vascular calcification density and calcific particle number were significantly greater in OVX than SHAM (8·4 ± 2·8 vs. 1·9 ± 0·6 mg cm,3, P = 0·042, and 94 ± 26 vs. 33 ± 7 particles cm,3, P = 0·046, respectively). Calcification morphology, as assessed by the arc angle subtended by the largest calcific particle, showed no difference between groups (OVX 33 ± 7° vs. SHAM 33 ± 5°, P = 0·99). By Western blot analysis, OVX increased the vascular OPG:RANKL ratio by 66%, P = 0·029, primarily by decreasing RANKL (P = 0·019). At month 9, MRI demonstrated no difference in atheroma volume between OVX and SHAM, and no significant change was seen by the end of the study. Conclusions, In contrast to bone, vascular OPG:RANKL ratio increased in response to ovariectomy with a corresponding fourfold increase in arterial calcification. This diametrical organ-specific response may explain the comorbid association of osteoporosis with calcifying atherosclerosis in post-menopausal women. [source] Development of renal bone diseaseEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2006A. Ferreira Abstract Renal osteodystrophy (ROD) develops as the early stages of chronic renal failure (CRF) and covers a spectrum of bone changes observed in the uraemic patient, which extend from high remodelling bone disease (frequently known as osteitis fibrosa) to low turnover, or adynamic disease. Between these two extremes there are also cases of bone mineralization compromised in variable degrees, as is the case of ,mixed bone disease' and osteomalacia. The dynamic process of bone remodelling is compromised in CRF, and a positive or negative bone balance can be observed in uraemic patients. In addition to the classic modulators of bone remodelling, like parathyroid hormone, calcitriol and calcitonin, other factors were recently identified as significant modulators of osteoblast and osteoclast activation in uraemic patients. In fact, different cytokines and growth factors, acting at an autocrine or paracrine level, seem to play a relevant role in the bone and mineral changes observed in uraemia. Recently, observations have been made of the development of more sensitive and specific techniques to assay different biochemical markers of bone turnover and mineral metabolism. Analogously, new contributions of conventional bone histology, bone immunocytochemistry and molecular biology, which enabled the understanding of some etiopathogenic mechanisms of ROD, were observed. [source] Osteoprotegerin and bone turnover markers in heavily pretreated HIV-infected patientsHIV MEDICINE, Issue 3 2005E Seminari Objectives To characterize osteoprotegerin (OPG) levels, bone remodelling and bone mineral density (BMD) in heavily pretreated HIV-infected patients on antiretroviral therapy, and to evaluate the clinical factors associated with bone density decline. Methods Heavily pretreated (>5 years) HIV-positive patients were enrolled in this cross-sectional, observational study, which was based on a total body bone densitometry examination and a comprehensive evaluation of bone and mineral parameters. Results Sixty-eight patients (55 male and 13 female) with a median age of 41 years (range 25,60 years) were included in the study. Their antiretroviral treatment lasted for 82 months. On the basis of the World Health Organization criteria, nine patients (13.2%) were osteoporotic [T-score<,2.5 standard deviation (SD)] and 19 patients (27.9%) were osteopenic (T-score between,1 and,2.5). The principal outcomes associated with the presence of a low BMD were high OPG and lysylpyridinoline/creatinine ratio (Dpd) values. Most of the patients (39 of 48; 81.25%) showed vitamin D insufficiency [Vitamin D (25(OH)D)<18 ng/mL] with secondary hyperparathyroidism (13 of 50 patients: 26%), which proved to be correlated to osteocalcin (BGP) levels [parathyroid hormone (PTH) vs. BGP: r=0.34; P<0.01]. There was an inverse correlation between T-scores and serum osteocalcin and alkaline phosphatase (AP) levels, on one hand, and Dpd, on the other. High AP and Dpd values were associated with relative risks of 4.1 [95% confidence interval (CI)=1.01,17.6] and 7.2 (95% CI=1.67,31.03), respectively, of a pathological T-score. Multivariate analysis revealed that the factors associated with the presence of osteopenia or osteoporosis were older age and lower body mass index. Conclusions About 40% of our heavily pretreated subjects with advanced HIV infection had a low BMD, and 56% (24 of 44 patients) showed a high bone turnover rate with marked osteoclast activation. High OPG levels may protect against bone resorption. [source] Relevance of a new rat model of osteoblastic metastases from prostate carcinoma for preclinical studies using zoledronic acidINTERNATIONAL JOURNAL OF CANCER, Issue 4 2008Franēois Lamoureux Abstract Animal models that mimic osteoblastic metastases associated with prostate carcinoma are required to improve the therapeutic options in humans. A new model was then developed and characterized in immunocompetent rats. The bisphosphonate zoledronic acid (ZOL) was tested to validate this model as a therapeutic application. Rat AT6-1 prostate tumor cells were characterized in vitro at the transcriptional (bone and epithelial markers) and functional (induction of mineralized nodules) levels. The bone lesions induced after their direct injection into the femur bone marrow were characterized by radiography, microscanner and histology analyses. ZOL effects were studied in vivo on bone lesion development and in vitro on AT6-1 cell proliferation, apoptosis and cell cycle analysis. Apart from epithelial markers, AT6-1 cells express an osteoblast phenotype as they express osteoblastic markers and are able to induce mineralized nodule formation in vitro. A disorganization of the trabecular bone at the growth zone level was observed in vivo after intraosseous AT6-1 cell injection as well as cortical erosion. The tumor itself is associated with bone formation as revealed by SEM analysis and polarized light microscopy. ZOL prevents the development of such osteoblastic lesions, related to a direct inhibitory effect on tumor cell proliferation independent of caspase 3 activation, but associated with cell cycle arrest. A new rat model of osteoblastic bone metastases was validated in immunocompetent rats and used to show the relevance of using ZOL in such lesions, as this compound shows bifunctional effects on both bone remodelling and tumor cell proliferation. © 2007 Wiley-Liss, Inc. [source] Porosity of human mandibular condylar boneJOURNAL OF ANATOMY, Issue 3 2007G. A. P. Renders Abstract Quantification of porosity and degree of mineralization of bone facilitates a better understanding of the possible effects of adaptive bone remodelling and the possible consequences for its mechanical properties. The present study set out first to give a three-dimensional description of the cortical canalicular network in the human mandibular condyle, in order to obtain more information about the principal directions of stresses and strains during loading. Our second aim was to determine whether the amount of remodelling was larger in the trabecular bone than in cortical bone of the condyle and to establish whether the variation in the amount of remodelling was related to the surface area of the cortical canals and trabeculae. We hypothesized that there were differences in porosity and orientation of cortical canals between various cortical regions. In addition, as greater cortical and trabecular porosities are likely to coincide with a greater surface area of cortical canals and trabeculae available for osteoblastic and osteoclastic activity, we hypothesized that this surface area would be inversely proportional to the degree of mineralization of cortical and trabecular bone, respectively. Micro-computed tomography was used to quantify porosity and mineralization in cortical and trabecular bone of ten human mandibular condyles. The cortical canals in the subchondral cortex of the condyle were orientated in the mediolateral direction, and in the anterior and posterior cortex in the superoinferior direction. Cortical porosity (average 3.5%) did not differ significantly between the cortical regions. It correlated significantly with the diameter and number of cortical canals, but not with cortical degree of mineralization. In trabecular bone (average porosity 79.3%) there was a significant negative correlation between surface area of the trabeculae and degree of mineralization; such a correlation was not found between the surface area of the cortical canals and the degree of mineralization of cortical bone. No relationship between trabecular and cortical porosity, nor between trabecular degree of mineralization and cortical degree of mineralization was found, suggesting that adaptive remodelling is independent and different between trabecular and cortical bone. We conclude (1) that the principal directions of stresses and strains are presumably directed mediolaterally in the subchondral cortex and superoinferiorly in the anterior and posterior cortex, (2) that the amount of remodelling is larger in the trabecular than in the cortical bone of the mandibular condyle; in trabecular bone variation in the amount of remodelling is related to the available surface area of the trabeculae. [source] Detecting microdamage in boneJOURNAL OF ANATOMY, Issue 2 2003T. C. Lee Abstract Fatigue-induced microdamage in bone contributes to stress and fragility fractures and acts as a stimulus for bone remodelling. Detecting such microdamage is difficult as pre-existing microdamage sustained in vivo must be differentiated from artefactual damage incurred during specimen preparation. This was addressed by bulk staining specimens in alcohol-soluble basic fuchsin dye, but cutting and grinding them in an aqueous medium. Nonetheless, some artefactual cracks are partially stained and careful observation under transmitted light, or epifluorescence microscopy, is required. Fuchsin lodges in cracks, but is not site-specific. Cracks are discontinuities in the calcium-rich bone matrix and chelating agents, which bind calcium, can selectively label them. Oxytetracycline, alizarin complexone, calcein, calcein blue and xylenol orange all selectively bind microcracks and, as they fluoresce at different wavelengths and colours, can be used in sequence to label microcrack growth. New agents that only fluoresce when involved in a chelate are currently being developed , fluorescent photoinduced electron transfer (PET) sensors. Such agents enable microdamage to be quantified and crack growth to be measured and are useful histological tools in providing data for modelling the material behaviour of bone. However, a non-invasive method is needed to measure microdamage in patients. Micro-CT is being studied and initial work with iodine dyes linked to a chelating group has shown some promise. In the long term, it is hoped that repeated measurements can be made at critical sites and microdamage accumulation monitored. Quantification of microdamage, together with bone mass measurements, will help in predicting and preventing bone fracture failure in patients with osteoporosis. [source] Bone adaptation to load: microdamage as a stimulus for bone remodellingJOURNAL OF ANATOMY, Issue 6 2002T. C. Lee Abstract Mechanical loading in the proximal radius was increased by ulnar osteotomy (Group O), altered by Steinmann pinning (Group P) or unaltered in sham operated controls (Group C) in skeletally mature female sheep, aged 2,4 years. A series of intravenous fluorochromes were given to label bone formation and fuchsin-stained microdamage assessed at intervals of up to 24 weeks. Microcracks were present in all groups and were found in the original cortex near the periosteal surface. No microcracks were found in the new, fibrolamellar bone laid down at periosteal or endosteal surfaces. Mean microcrack length (49 µm, SD 10 µm) did not differ between groups or over time. Microcrack numerical and surface densities and resorption cavity density peaked in all groups at 6 weeks, consistent with a regional acceleratory phenomenon (RAP), but the peaks were significantly greater in Group O. The density of refilling or secondary osteons peaked at 10 weeks and the mean time required for the formation of an osteon was 7.51 ± 0.59 weeks. Fatigue-induced microdamage is normally present in bone and is increased due to repetitive loading of the mechanically overloaded radius. The location and timing of microcracks, resorption cavities and secondary osteons are consistent with the activation-resorption-formation remodelling cycle and suggest that microdamage is a stimulus for bone remodelling. [source] If bone is the answer, then what is the question?JOURNAL OF ANATOMY, Issue 2 2000R. HUISKES In the 19th century, several scientists attempted to relate bone trabecular morphology to its mechanical, load-bearing function. It was suggested that bone architecture was an answer to requirements of optimal stress transfer, pairing maximal strength to minimal weight, according to particular mathematical design rules. Using contemporary methods of analysis, stress transfer in bones was studied and compared with anatomical specimens, from which it was hypothesised that trabecular architecture is associated with stress trajectories. Others focused on the biological processes by which trabecular architectures are formed and on the question of how bone could maintain the relationship between external load and architecture in a variable functional environment. Wilhelm Roux introduced the principle of functional adaptation as a self-organising process based in the tissues. Julius Wolff, anatomist and orthopaedic surgeon, entwined these 3 issues in his book The Law of Bone Remodeling (translation), which set the stage for biomechanical research goals in our day. ,Wolff's Law' is a question rather than a law, asking for the requirements of structural optimisation. In this article, based on finite element analysis (FEA) results of stress transfer in bones, it is argued that it was the wrong question, putting us on the wrong foot. The maximal strength/minimal weight principle does not provide a rationale for architectural formation or adaptation; the similarity between trabecular orientation and stress trajectories is circumstantial, not causal. Based on computer simulations of bone remodelling as a regulatory process, governed by mechanical usage and orchestrated by osteocyte mechanosensitivity, it is shown that Roux's paradigm, conversely, is a realistic proposition. Put in a quantitative regulatory context, it can predict both trabecular formation and adaptation. Hence, trabecular architecture is not an answer to Wolff's question, in the sense of this article's title. There are no mathematical optimisation rules for bone architecture; there is just a biological regulatory process, producing a structure adapted to mechanical demands by the nature of its characteristics, adequate for evolutionary endurance. It is predicted that computer simulation of this process can help us to unravel its secrets. [source] Alveolar ridge augmentation using implants coated with recombinant human bone morphogenetic protein-7 (rhBMP-7/rhOP-1): histological observationsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 6 2010Cristiano Susin Susin C, Qahash M, Polimeni G, Lu PH, Prasad HS, Rohrer MD, Hall J, Wikesjö UME. Alveolar ridge augmentation using implants coated with recombinant human bone morphogenetic protein-7 (rhBMP-7/rhOP-1): histological observations. J Clin Periodontol 2010; 37: 574,581. doi: 10.1111/j.1600-051X.2010.01554.x. Abstract Background: Pre-clinical studies have shown that recombinant human bone morphogenetic protein-2 (rhBMP-2) coated onto purpose-designed titanium porous-oxide surface implants induces clinically relevant bone formation and osseointegration. The objective of this study was to examine the potential of rhBMP-7, also known as recombinant human osteogenic protein-1 (rhOP-1), coated onto titanium porous-oxide surface implants to support vertical alveolar ridge augmentation and implant osseointegration. Materials and Methods: Bilateral, critical-size, 5 mm, supraalveolar peri-implant defects were created in six young adult Hound Labrador mongrel dogs. The animals received implants coated with rhBMP-7 at 1.5 or 3.0 mg/ml randomized to contra-lateral jaw quadrants. The mucoperiosteal flaps were advanced, adapted, and sutured to submerge the implants for primary intention healing. The animals received fluorescent bone markers at 3, 4, 7, and 8 weeks post-surgery when they were euthanized for histological evaluation. Results: Without striking differences between treatments, the implant sites exhibited a swelling that gradually regressed to become hard to palpation disguising the implant contours. The histological evaluation showed robust bone formation; the newly formed bone assuming characteristics of the contiguous resident bone, bone formation (height and area) averaging 4.1±1.0 versus 3.6±1.7 mm and 3.6±1.9 versus 3.1±1.8 mm2; and bone density 56%versus 50% for implants coated with rhBMP-7 at 1.5 and 3.0 mg/ml, respectively. Both treatments exhibited clinically relevant osseointegration, the corresponding bone,implant contact values averaging 51% and 47%. Notable peri-implant resident bone remodelling was observed for implants coated with rhBMP-7 at 3.0 mg/ml. Conclusions: rhBMP-7 coated onto titanium porous-oxide surface implants induces clinically relevant local bone formation including osseointegration and vertical augmentation of the alveolar ridge, the higher concentration/dose associated with some local side effects. [source] Evaluation of implants coated with rhBMP-2 using two different coating strategies: a critical-size supraalveolar peri-implant defect study in dogsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 6 2010Jaebum Lee Lee J, Decker JF, Polimeni G, Cortella CA, Rohrer MD, Wozney JM, Hall J, Susin C, Wikesjö UME. Evaluation of implants coated with rhBMP-2 using two different coating strategies: a critical-size supraalveolar peri-implant defect study in dogs. J Clin Periodontol 2010; 37: 582,590. doi: 10.1111/j.1600-051X.2010.01557.x. Abstract Background: Implants coated with recombinant human bone morphogenetic protein-2 (rhBMP-2) induce relevant bone formation but also resident bone remodelling. Objectives: To compare the effect of implants fully or partially coated with rhBMP-2 on new bone formation and resident bone remodelling. Materials and Methods: Twelve, male, adult, Hound Labrador mongrel dogs were used. Critical-size, supraalveolar, peri-implant defects received titanium porous oxide surface implants coated in their most coronal aspect with rhBMP-2 (coronal-load/six animals) or by immersion of the entire implant in an rhBMP-2 solution (soak-load/six animals) for a total of 30 ,g rhBMP-2/implant. All implants were air-dried. The animals were euthanized at 8 weeks for histometric evaluation. Results: Clinical healing was uneventful. Supraalveolar bone formation was not significantly affected by the rhBMP-2 application protocol. New bone height and area averaged (± SE) 3.4 ± 0.2 versus 3.5 ± 0.4 mm and 2.6 ± 0.4 versus 2.5 ± 0.7 mm2 for coronal-load and soak-load implants, respectively (p>0.05). The corresponding bone density and bone,implant contact (BIC) recordings averaged 38.0 ± 3.8%versus 34.4 ± 5.6% and 25.0 ± 3.8%versus 31.2 ± 3.3% (p>0.05). In contrast, resident bone remodelling was significantly influenced by the rhBMP-2 application protocol. Bone density outside the implants threads averaged 74.7 ± 3.8% and 50.8 ± 4.1% for coronal-load and soak-load implants, respectively (p<0.05); bone density within the thread area averaged 51.8 ± 1.2% and 37.8 ± 2.9%, and BIC 70.1 ± 6.7% and 43.3 ± 3.9% (p<0.05). Conclusion: Local application of rhBMP-2 appears to be a viable technology to support local bone formation and osseointegration. Coronal-load implants obviate resident bone remodelling without compromising new bone formation. [source] Stability of crestal bone level at platform-switched non-submerged titanium implants: a histomorphometrical study in dogsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 6 2009Jürgen Becker Abstract Objectives: To investigate the influence of platform switching on crestal bone level changes at non-submerged titanium implants over a period of 6 months. Material and Methods: Titanium implants (n=72) were placed at 0.4 mm above the alveolar crest in the lower jaws of 12 dogs and randomly assigned to either matching or non-matching (circumferential horizontal mismatch of 0.3 mm) healing abutments. At 4, 8, 12, and 24 weeks, dissected blocks were processed for histomorphometrical analysis. Measurements were made between the implant shoulder (IS) and the apical extension of the long junctional epithelium (aJE), the most coronal level of bone in contact with the implant (CLB), and the level of the alveolar bone crest (BC). Results: At 24 weeks, differences in the mean IS,aJE, IS,CLB, and IS,BC values were 0.2 ± 1.2, 0.3 ± 0.7, and 0.3 ± 0.8 mm at the buccal aspect, and 0.2 ± 0.9, 0.3 ± 0.5, and 0.3 ± 0.8 mm at the lingual aspect, respectively. Comparisons between groups revealed no significant differences at either the buccal or the lingual aspects. Conclusions: It was concluded that (i) bone remodelling was minimal in both groups and (ii) platform switching may not be of crucial importance for maintenance of the crestal bone level. [source] Alveolar ridge augmentation using implants coated with recombinant human bone morphogenetic protein-2: histologic observationsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 11 2008Ulf M. E. Wikesjö Abstract Background: Studies using ectopic rodent, orthotopic canine, and non-human primate models show that bone morphogenetic proteins (BMPs) coated onto titanium surfaces induce local bone formation. The objective of this study was to examine the ability of recombinant human BMP-2 (rhBMP-2) coated onto a titanium porous oxide implant surface to stimulate local bone formation including osseointegration and vertical augmentation of the alveolar ridge. Material and Methods: Bilateral, critical-size, 5 mm, supra-alveolar, peri-implant defects were created in 12 young adult Hound Labrador mongrel dogs. Six animals received implants coated with rhBMP-2 at 0.75 or 1.5 mg/ml, and six animals received implants coated with rhBMP-2 at 3.0 mg/ml or uncoated control. Treatments were randomized between jaw quadrants. The mucoperiosteal flaps were advanced, adapted and sutured to submerge the implants for primary intention healing. The animals received fluorescent bone markers at weeks 3, 4, 7 and 8 post-surgery when they were euthanized for histologic evaluation. Results: Jaw quadrants receiving implants coated with rhBMP-2 exhibited gradually regressing swelling that became hard to palpate disguising the contours of the implants. The histologic evaluation showed robust bone formation reaching or exceeding the implant platform. The newly formed bone exhibited characteristics of the adjoining resident Type II bone including cortex formation for sites receiving implants coated with rhBMP-2 at 0.75 or 1.5 mg/ml. Sites receiving implants coated with rhBMP-2 at 3.0 mg/ml exhibited more immature trabecular bone formation, seroma formation and peri-implant bone remodelling resulting in undesirable implant displacement. Control implants exhibited minimal, if any, bone formation. Thus, implants coated with rhBMP-2 at 0.75, 1.5 and 3.0 mg/ml exhibited significant bone formation (height and area) compared with the sham-surgery control averaging (±SD) 4.4±0.4, 4.2±0.7 and 4.2±1.2 versus 0.8±0.3 mm; and 5.0±2.2, 5.6±2.2 and 7.4±3.5 versus 0.7±0.3 mm2, respectively (p<0.01). All the treatment groups exhibited clinically relevant osseointegration. Conclusions: rhBMP-2 coated onto titanium porous oxide implant surfaces induced clinically relevant local bone formation including vertical augmentation of the alveolar ridge and osseointegration. Higher concentrations/doses were associated with untoward effects. [source] Biological mediators and periodontal regeneration: a review of enamel matrix proteins at the cellular and molecular levelsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 2008Dieter D. Bosshardt Abstract Background: Despite a large body of clinical and histological data demonstrating beneficial effects of enamel matrix proteins (EMPs) for regenerative periodontal therapy, it is less clear how the available biological data can explain the mechanisms underlying the supportive effects of EMPs. Objective: To analyse all available biological data of EMPs at the cellular and molecular levels that are relevant in the context of periodontal wound healing and tissue formation. Methods: A stringent systematic approach was applied using the key words "enamel matrix proteins" OR "enamel matrix derivative" OR "emdogain" OR "amelogenin". The literature search was performed separately for epithelial cells, gingival fibroblasts, periodontal ligament cells, cementoblasts, osteogenic/chondrogenic/bone marrow cells, wound healing, and bacteria. Results: A total of 103 papers met the inclusion criteria. EMPs affect many different cell types. Overall, the available data show that EMPs have effects on: (1) cell attachment, spreading, and chemotaxis; (2) cell proliferation and survival; (3) expression of transcription factors; (4) expression of growth factors, cytokines, extracellular matrix constituents, and other macromolecules; and (5) expression of molecules involved in the regulation of bone remodelling. Conclusion: All together, the data analysis provides strong evidence for EMPs to support wound healing and new periodontal tissue formation. [source] Changes in vertebral structure during growth of reared rainbow trout, Oncorhynchus mykiss (Walbaum): a new approach using modelling of vertebral bone profilesJOURNAL OF FISH DISEASES, Issue 3 2009M-H Deschamps Abstract Severe bone resorption of the vertebral body in reared rainbow trout was thought to be a dysfunction in mineral balance induced by increased growth rate in unfavourable rearing conditions. To verify this assumption, we sampled market-sized trout (c. 250 g) from 20 fish farms with different rearing conditions. Growth rate was also studied by sampling trout reared in three different water temperatures from fry to market-size. Transverse sections of vertebrae were microradiographed, then digitized. Total bone area (Tt-B.Ar.) and bone profiles were obtained using BONE PROFILER 3.23 software and a mathematical model was developed to statistically compare bone profiles using 12 parameters in four vertebra regions. Tt-B.Ar. and bone profiles were found to vary with rearing conditions and growing temperatures, indicating obvious influences of these factors on bone remodelling. However, vertebral resorption was found to be a general phenomenon. In trout from 190 to 235 mm in length, vertebrae underwent important remodelling resulting in large resorption of the middle area, while the transition and peripheral areas showed an increase in bone deposition. Changes in vertebra architecture seem to be a good compromise between the need to mobilize stored minerals during growth while maintaining vertebral biomechanical properties. [source] Femur window,a new approach to microcirculation of living bone in situJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2005N. Hansen-Algenstaedt Abstract Background: The processes of osteogenesis, bone remodelling, fracture repair and metastasis to bone are determined by complex sequential interactions involving cellular and microcirculatory parameters. Consequently studies targeting the analysis of microcirculatory parameters on such processes should mostly respect these complex conditions. However these conditions could not yet be achieved in vitro and therefore techniques that allow a long-term observation of functional and structural parameters of microcirculation in bone in vivo at a high spatial resolution are needed to monitor dynamic events, such as fracture healing, bone remodelling and tumor metastasis. Methods: We developed a bone chamber implant (femur window) for long-term intravital microscopy of pre-existing bone and its microcirculation at an orthotopic site in mice preserving the mechanical properties of bone. After bone chamber implantation vascular density, vessel diameter, vessel perfusion, vascular permeability and leukocyte-endothelial interactions (LEIs) in femoral bone tissue of c57-black mice (n = 11) were measured quantitatively over 12 days using intravital fluorescence microscopy. Furthermore a model for bone defect healing and bone metastasis in the femur window was tested. Results: Microvascular permeability and LEIs showed initially high values after chamber implantation followed by a significant decrease to a steady state at day 6 and 12, whereas structural parameters remained unaltered. Bone defect healing and tumor growth was observed over 12 and 90 days respectively. Conclusion: The new femur window design allows a long-term analysis of structural and functional properties of bone and its microcirculation quantitatively at a high spatial resolution. Altered functional parameters of microcirculation after surgical procedures and their time dependent return to a steady state underline the necessity of long-term observations to achieve unaltered microcirculatory parameters. Dissection of the complex interactions between bone and microcirculation enables us to evaluate physiological and pathological processes of bone and may give new insights especially in dynamic events e.g. fracture healing, bone remodeling and tumor metastasis. © 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Localization of SOST/sclerostin in cementocytes in vivo and in mineralizing periodontal ligament cells in vitroJOURNAL OF PERIODONTAL RESEARCH, Issue 2 2010A. Jäger Jäger A, Götz W, Lossdörfer S, Rath-Deschner B. Localization of SOST/sclerostin in cementocytes in vivo and in mineralizing periodontal ligament cells in vitro. J Periodont Res 2009; doi: 10.1111/j.1600-0765.2009.01227.x. © 2009 John Wiley & Sons A/S Background and Objective:, Cementum and bone are rather similar hard tissues, and osteocytes and cementocytes, together with their canalicular network, share many morphological and cell biological characteristics. However, there is no clear evidence that cementocytes have a function in tissue homeostasis of cementum comparable to that of osteocytes in bone. Recent studies have established an important role for the secreted glycoprotein sclerostin, the product of the SOST gene, as an osteocyte-derived signal to control bone remodelling. In this study, we investigated the expression of sclerostin in cementocytes in vivo as well as the expression of SOST and sclerostin in periodontal ligament cell cultures following induction of mineralization. Material and Method:, Immunolocalization of sclerostin was performed in decalcified histological sections of mouse and human teeth and alveolar bone. Additionally, periodontal ligament cells from human donors were cultured in osteogenic conditions, namely in the presence of dexamethasone, ascorbic acid and ,-glycerophosphate, for up to 3 wk. The induction of calcified nodules was visualized by von Kossa stain. SOST mRNA was detected by real-time PCR, and the presence of sclerostin was verified using immunohistochemistry and western blots. Results:, Expression of sclerostin was demonstrated in osteocytes of mouse and human alveolar bone. Distinct immunolocalization in the cementocytes was shown. In periodontal ligament cultures, following mineralization treatment, increasing levels of SOST mRNA as well as of sclerostin protein could be verified. Conclusion:, The identification of SOST/sclerostin in cementocytes and mineralizing periodontal ligament cells adds to our understanding of the biology of the periodontium, but the functional meaning of these findings can only be unravelled after additional in vitro and in vivo studies. [source] Treatment of a prolapsed lumbar intervertebral disc in a ferretJOURNAL OF SMALL ANIMAL PRACTICE, Issue 10 2004D. Lu A seven-month-old, male ferret had acute paraplegia and radiographs showed signs of disc prolapse between the second and third lumbar vertebrae (L2/3). Hemilaminectomy was performed to decompress the spinal cord. Histological examination revealed that the extradural material was consistent with annulus fibrosus and the L2/3 articular facets were enlarged as a result of bone remodelling. The ferret became ambulatory one month postoperatively. Five months postoperatively, the ferret had normal posture with mild proprioceptive deficits in the pelvic limbs, and fusion of the L2 and L3 vertebral bodies. [source] Multiple root resorption as a presenting sign of Paget's disease of boneORAL SURGERY, Issue 1 2008M. Monteiro Abstract Paget's disease is a chronic disorder of bone remodelling of uncertain aetiology. Its craniofacial manifestions may be the first indicators of disease. We present an unusual case of Paget's disease presenting with significant external root resorption. The oral manifestions and radiological features of Paget's disease as well as the implications for surgery in the mouth are discussed. [source] Finite Element Modelling of Bioactive Contact in Bone-Implant InterfacePROCEEDINGS IN APPLIED MATHEMATICS & MECHANICS, Issue 1 2008André Lutz Finite element simulation for the prediction of bone remodelling caused by implants is a powerful method to improve or to rate implant designs even before they will be evaluated in clinical studies. But the bone,implant interaction is often modelled as ideal bonding in the interface. This approach is not suitable to describe the interrelation of both parts in a physiological manner. To correct these insufficiencies a 3D bioactive contact element has been developed. This contact element describes on the one hand the pure mechanical interaction and on the other hand the mechanical stimulated bone ingrowth in porous surfaces. The benefits of the use of the bioactive contact element regarding the standard method will be presented in this contribution. A comparison of both methods based on clinic results regarding a hip prosthesis with mixed surface textures will be shown. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Opacity and Lucency Sign of the Seventh Lumbar Vertebra in DogsANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 5 2010S. Kneissl With 2 figures Summary A curvilinear opacity of the seventh vertebral arch and an adjacent focal lucency of the seventh lumbar vertebral body were incidentally noted in routine radiographs. The aim of this study was to analyze this radiographic absorption pattern using a sample of 51 dogs. Images of the bony surface of three macerated lumbosacral junctions were compared to their laterolateral radiographs and computed tomographic (CT) scans. Additional 48 lateral radiographic projections were reviewed for presence or absence of L7 opacity and lucency, length of the L6 and L7 vertebral bodies, vertebral disc disease, osteochondrosis, or spondylosis. Retrieved data were compiled and statistically analyzed. Radiographs and CT scans of the macerated bones revealed that the L7 pedicle had thickened layers of compact bone and the adjacent vertebral notch varying depth and extension. Superimposition of the pedicle on the vertebral body resulted in a curvilinear opacity (L7 opacity), the vertebral notch caused the focal lucency (L7 lucency). These findings were present in 69% of the reviewed radiographs and were found to be significantly associated with L6,L7 length ratios of less than 0.86 (P = 0.003). It is hypothesized that the changes correspond with normal anatomic morphology of the seventh lumbar vertebra plus adaptive bone remodelling. The importance of this study is that it could help avoid misinterpretation of this appearance as a pathologic condition. [source] A comparative view on mechanisms and functions of skeletal remodelling in teleost fish, with special emphasis on osteoclasts and their functionBIOLOGICAL REVIEWS, Issue 2 2009P. Eckhard Witten ABSTRACT Resorption and remodelling of skeletal tissues is required for development and growth, mechanical adaptation, repair, and mineral homeostasis of the vertebrate skeleton. Here we review for the first time the current knowledge about resorption and remodelling of the skeleton in teleost fish, the largest and most diverse group of extant vertebrates. Teleost species are increasingly used in aquaculture and as models in biomedical skeletal research. Thus, detailed knowledge is required to establish the differences and similarities between mammalian and teleost skeletal remodelling, and between distantly related species such as zebrafish (Danio rerio) and medaka (Oryzias latipes). The cellular mechanisms of differentiation and activation of osteoclasts and the functions of teleost skeletal remodelling are described. Several characteristics, related to skeletal remodelling, distinguish teleosts from mammals. These characteristics include (a) the absence of osteocytes in most species; (b) the absence of haematopoietic bone marrow tissue; (c) the abundance of small mononucleated osteoclasts performing non-lacunar (smooth) bone resorption, in addition to or instead of multinucleated osteoclasts; and (d) a phosphorus- rather than calcium-driven mineral homeostasis (mainly affecting the postcranial dermal skeleton). Furthermore, (e) skeletal resorption is often absent from particular sites, due to sparse or lacking endochondral ossification. Based on the mode of skeletal remodelling in early ontogeny of all teleosts and in later stages of development of teleosts with acellular bone we suggest a link between acellular bone and the predominance of mononucleated osteoclasts, on the one hand, and cellular bone and multinucleated osteoclasts on the other. The evolutionary origin of skeletal remodelling is discussed and whether mononucleated osteoclasts represent an ancestral type of resorbing cells. Revealing the differentiation and activation of teleost skeletal resorbing cells, in the absence of several factors that trigger mammalian osteoclast differentiation, is a current challenge. Understanding which characters of teleost bone remodelling are derived and which characters are conserved should enhance our understanding of the process in fish and may provide insights into alternative pathways of bone remodelling in mammals. [source] Crystallization and preliminary X-ray analysis of mouse RANK and its complex with RANKLACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 6 2009Thomas S. Walter The interaction between the TNF-family molecule receptor activator of NF-,B ligand (RANKL) and its receptor RANK induces osteoclast formation, activation and survival in the process of bone remodelling. RANKL,RANK also plays critical roles in T-cell/dendritic cell communication and lymph-node formation and in a variety of pathologic conditions such as tumour-cell migration and bone metastasis. Both the ectodomain of mouse RANKL and the extracellular domain of mouse RANK have been cloned, expressed and purified. Crystals of RANK alone and of RANK in complex with RANKL have been obtained that are suitable for structure determination. [source] Bortezomib reduces serum dickkopf-1 and receptor activator of nuclear factor- ,B ligand concentrations and normalises indices of bone remodelling in patients with relapsed multiple myelomaBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2006Evangelos Terpos Summary The effect of bortezomib on bone remodelling was evaluated in 34 relapsed myeloma patients. At baseline, patients had increased serum concentrations of dickkopf-1 (DKK-1), soluble receptor activator of nuclear factor- ,B ligand (sRANKL), sRANKL/osteoprotegerin ratio, C-telopeptide of type-I collagen (CTX) and tartrate-resistant acid phosphatase isoform-5b (TRACP-5b); bone-alkaline phosphatase and osteocalcin were reduced. Serum DKK-1 correlated with CTX and severe bone disease. Bortezomib administration significantly reduced serum DKK-1, sRANKL, CTX, and TRACP-5b after four cycles, and dramatically increased bone-alkaline phosphatase and osteocalcin, irrespective of treatment response. This is the first study showing that bortezomib reduces DKK-1 and RANKL serum levels, leading to the normalisation of bone remodelling in relapsed myeloma. [source] Emerging pharmacology and physiology of neuromedin U and the structurally related peptide neuromedin SBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2009JD Mitchell Neuromedin U (NMU) has been paired with the G-protein-coupled receptors (GPRs) NMU1 (formely designated as the orphan GPR66 or FM-3) and NMU2 (FM-4 or hTGR-1). Recently, a structurally related peptide, neuromedin S (NMS), which shares an amidated C-terminal heptapeptide motif, has been identified in both rat and human, and has been proposed as a second ligand for these receptors. Messenger RNA encoding NMU receptor subtypes shows differential expression: NMU1 is predominantly expressed in peripheral tissues, particularly the gastrointestinal tract, whereas NMU2 is abundant within the brain and spinal cord. NMU peptide parallels receptor distribution with highest expression in the gastrointestinal tract and specific structures within the brain, reflecting its major role in the regulation of energy balance. The NMU knockout mouse has an obese phenotype and, in agreement, the Arg165Trp amino acid variant of NMU-25 in humans, which is functionally inactive, co-segregated with childhood-onset obesity. Emerging physiological roles for NMU include vasoconstriction mediated predominantly via NMU1 with nociception and bone remodelling via NMU2. The NMU system has also been implicated in the pathogenesis of septic shock and cancers including bladder carcinoma and acute myeloid leukaemia. Intriguingly, NMS is more potent at NMU2 receptors in vivo where it has similar central actions in suppression of feeding and regulation of circadian rhythms to NMU. Taken together with its vascular actions, NMU may be a functional link between energy balance and the cardiovascular system and may provide a future target for therapies directed against the disorders that comprise metabolic syndrome. [source] An endogenous regulator of inflammation, resolvin E1, modulates osteoclast differentiation and bone resorptionBRITISH JOURNAL OF PHARMACOLOGY, Issue 8 2008B S Herrera Background and purpose: The inflammation-resolving lipid mediator resolvin E1 (RvE1) effectively stops inflammation-induced bone loss in vivo in experimental periodontitis. It was of interest to determine whether RvE1 has direct actions on osteoclast (OC) development and bone resorption. Experimental approach: Primary OC cultures derived from mouse bone marrow were treated with RvE1 and analysed for OC differentiation, cell survival and bone substrate resorption. Receptor binding was measured using radiolabelled RvE1. Nuclear factor (NF)-,B activation and Akt phosphorylation were determined with western blotting. Lipid mediator production was assessed with liquid chromatography tandem mass spectrometry. Key results: OC growth and resorption pit formation were markedly decreased in the presence of RvE1. OC differentiation was inhibited by RvE1 as demonstrated by decreased number of multinuclear OC, a delay in the time course of OC development and attenuation of receptor activator of NF-,B ligand-induced nuclear translocation of the p50 subunit of NF-,B. OC survival and apoptosis were not altered by RvE1. Messenger RNA for both receptors of RvE1, ChemR23 and BLT1 is expressed in OC cultures. Leukotriene B4 (LTB4) competed with [3H]RvE1 binding on OC cell membrane preparations, and the LTB4 antagonist U75302 prevented RvE1 inhibition of OC growth, indicating that BLT1 mediates RvE1 actions on OC. Primary OC synthesized the RvE1 precursor 18R -hydroxy-eicosapentaenoic acid and LTB4. Co-incubation of OC with peripheral blood neutrophils resulted in transcellular RvE1 biosynthesis. Conclusions and implications: These results indicate that RvE1 inhibits OC growth and bone resorption by interfering with OC differentiation. The bone-sparing actions of RvE1 are in addition to inflammation resolution, a direct action in bone remodelling. British Journal of Pharmacology (2008) 155, 1214,1223; doi:10.1038/bjp.2008.367; published online 22 September 2008 [source] Effect of low molecular weight heparin (dalteparin) and fondaparinux (Arixtra®) on human osteoblasts in vitro,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 2 2005A. E. Handschin Background: The prolonged administration of heparin for prevention and treatment of venous thromboembolism has been associated with a risk of heparin-induced osteoporosis. Fondaparinux is a new antithrombotic drug that specifically inhibits factor Xa. Because of the known interactions of other antithrombotic agents with bone remodelling, the effects of fondaparinux on human osteoblasts were analysed in vitro. Methods: Primary human osteoblast cell cultures were incubated with either the low molecular weight heparin dalteparin at concentrations of 30, 300 and 900 µg/ml or with fondaparinux at concentrations of 25, 50, 100, 150, 200 and 250 µg/ml. Cellular proliferation rate and protein synthesis were measured. Expression of genes encoding osteocalcin, collagen type I and alkaline phosphatase was examined by reverse transcriptase,polymerase chain reaction. Results: Incubation with dalteparin led to a significant, dose-dependent inhibition of osteoblast proliferation, inhibition of protein synthesis, and inhibited expression of phenotype markers (osteocalcin and alkaline phosphatase genes) after 3 and 7 days. No inhibitory effects were observed in the fondaparinux-treated cells. Conclusion: Fondaparinux did not inhibit osteoblast proliferation in vitro and may reduce the risk of heparin-induced osteoporosis associated with long-term heparin administration. Copyright © 2004 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] REVIEW ARTICLE: Reducing fracture risk with calcium and vitamin DCLINICAL ENDOCRINOLOGY, Issue 3 2010Paul Lips Summary Studies of vitamin D and calcium for fracture prevention have produced inconsistent results, as a result of different vitamin D status and calcium intake at baseline, different doses and poor to adequate compliance. This study tries to define the types of patients, both at risk of osteoporosis and with established disease, who may benefit from calcium and vitamin D supplementation. The importance of adequate compliance in these individuals is also discussed. Calcium and vitamin D therapy has been recommended for older persons, either frail and institutionalized or independent, with key risk factors including decreased bone mineral density (BMD), osteoporotic fractures, increased bone remodelling as a result of secondary hyperparathyroidism and increased propensity to falls. In addition, treatment of osteoporosis with a bisphosphonate was less effective in patients with vitamin D deficiency. Calcium and vitamin D supplementation is a key component of prevention and treatment of osteoporosis unless calcium intake and vitamin D status are optimal. For primary disease prevention, supplementation should be targeted to those with dietary insufficiencies. Several serum 25-hydroxyvitamin D (25(OH)D) cut-offs have been proposed to define vitamin D insufficiency (as opposed to adequate vitamin D status), ranging from 30 to 100 nmol/l. Based on the relationship between serum 25(OH)D, BMD, bone turnover, lower extremity function and falls, we suggest that 50 nmol/l is the appropriate serum 25(OH)D threshold to define vitamin D insufficiency. Supplementation should therefore generally aim to increase 25(OH)D levels within the 50,75 nmol/l range. This level can be achieved with a dose of 800 IU/day vitamin D, the dose that was used in succesfull fracture prevention studies to date; a randomized clinical trial assessing whether higher vitamin D doses achieve a greater reduction of fracture incidence would be of considerable interest. As calcium balance is not only affected by vitamin D status but also by calcium intake, recommendations for adequate calcium intake should also be met. The findings of community-based clinical trials with vitamin D and calcium supplementation in which compliance was moderate or less have often been negative, whereas studies in institutionalized patients in whom medication administration was supervised ensuring adequate compliance demonstrated significant benefits. [source] The use of molecular markers of bone turnover in the management of patients with metastatic bone diseaseCLINICAL ENDOCRINOLOGY, Issue 6 2008Markus J. Seibel Summary Biochemical markers of bone turnover are widely used in clinical practice. These indices have been shown to be associated with the occurrence, prognosis and therapeutic response of malignant bone lesions. For example, markers of bone resorption are often elevated in patients with established bone metastases and while this may point to a role of these markers in the diagnostic workup of cancer patients, the available evidence does not permit any final conclusions as to the accuracy and validity of the presently used markers in the early diagnosis of bone metastases. Many bone turnover markers appear to respond to antiresorptive and antineoplastic therapies, and recent evidence from prospective trials suggests that the aim of bisphosphonate therapy should be to normalize rates of bone remodelling to optimize therapeutic and prognostic outcomes. However, it remains unknown whether the use of bone markers in the routine clinical setting has any defined beneficial effects on overall outcome in cancer patients. Clearly, bone turnover markers have insufficient diagnostic or prognostic value to be used in isolation; however, the combination of these markers with other diagnostic techniques may improve clinical assessment of patients with bone-seeking cancers. This article reviews the available evidence (as of August 2007) on the clinical use of bone turnover markers in the management of patients with metastatic bone disease. [source] Mechanisms of osteoporosis in spinal cord injuryCLINICAL ENDOCRINOLOGY, Issue 5 2006Sheng-Dan Jiang Summary Osteoporosis is a known complication of spinal cord injury (SCI), but its mechanism remains unknown. The pathogenesis of osteoporosis after SCI is generally considered disuse. However, although unloading is an important factor in the pathogenesis of osteoporosis after SCI, neural lesion and hormonal changes also seem to be involved in this process. Innervation and neuropeptides play an important role in normal bone remodelling. SCI results in denervation of the sublesional bones and the neural lesion itself may play a pivotal role in the development of osteoporosis after SCI. Although upper limbs are normally loaded and innervated, bone loss also occurs in the upper extremities in patients with paraplegia, indicating that hormonal changes may be associated with osteoporosis after SCI. SCI-mediated hormonal changes may contribute to osteoporosis after SCI by different mechanisms: (1) increased renal elimination and reduced intestinal absorption of calcium leading to a negative calcium balance; (2) vitamin D deficiency plays a role in the pathogenesis of SCI-induced osteoporosis; (3) SCI antagonizes gonadal function and inhibits the osteoanabolic action of sex steroids; (4) hyperleptinaemia after SCI may contribute to the development of osteoporosis; (5) pituitary suppression of TSH may be another contributory factor to bone loss after SCI; and (6) bone loss after SCI may be caused directly, at least in part, by insulin resistance and IGFs. Thus, oversupply of osteoclasts relative to the requirement for bone resorption and/or undersupply of osteoblasts relative to the requirement for cavity repair results in bone loss after SCI. Mechanisms for the osteoporosis following SCI include a range of systems, and osteoporosis after SCI should not be simply considered as disuse osteoporosis. Unloading, neural lesion and hormonal changes after SCI result in severe bone loss. The aim of this review is to improve understanding with regard to the mechanisms of osteoporosis after SCI. The understanding of the pathogenesis of osteoporosis after SCI can help in the consideration of new treatment strategies. Because bone resorption after SCI is very high, intravenous bisphosphonates and denosumab should be considered for the treatment of osteoporosis after SCI. [source] | |||||||||||||||||||