Reconstruction of maxillary ridge atrophy caused by dentoalveolar trauma, using autogenous block bone graft harvested from chin: a case report

Background Dentoalveolar trauma, especially when involving front teeth, negatively affect the patient’s life; in particular, tooth avulsion is a complex injury that affects multiple tissues, and no treatment option offers stable long-term outcomes. The aim of this study was to report a case of reconstruction of atrophic anterior alveolar ridge after tooth loss, performed with autograft harvested from the chin, and subsequent prosthetic rehabilitation with the use of an osseointegrated implant. Case report A 23-years-old Caucasian girl, presented an atrophic alveolar bone in the area of tooth 11, as a result of tooth resorption 10 years after a tooth reimplantation procedure. Reconstruction was performed with autogenous bone harvested from the chin. After 6-months healing period to allow autograft incorporation, a dental implant was inserted. After further 6- months, a screw-retained implant supported metal-ceramic prosthesis was fabricated. Results The prosthetic rehabilitation was successful, and after a follow-up period of 5 years, the achieved result was stable.Conclusion It can be concluded that the autogenous bone graft harvested from the chin, is a safe and effective option for alveolar ridge defects reconstruction, allowing a subsequent placement of a dental implant supporting a prosthetic restoration.

Buccal Bone Plate Remodeling After Immediate Implant Placement With and Without Synthetic Bone Grafting and Flapless Surgery: Radiographic Study in Dogs

Recent studies in animals have shown pronounced resorption of the buccal bone plate after immediate implantation. The use of flapless surgical procedures prior to the installation of immediate implants, as well as the use of synthetic bone graft in the gaps represent viable alternatives to minimize buccal bone resorption and to favor osseointegration. The aim of this study was to evaluate the healing of the buccal bone plate following immediate implantation using the flapless approach, and to compare this process with sites in which a synthetic bone graft was or was not inserted into the gap between the implant and the buccal bone plate. Lower bicuspids from 8 dogs were bilaterally extracted without the use of flaps, and 4 implants were installed in the alveoli in each side of the mandible and were positioned 2.0 mm from the buccal bone plate (gap). Four groups were devised: 2.0-mm subcrestal implants (3.3 x 8 mm) using bone grafts (SCTG), 2.0-mm subcrestal implants without bone grafts (SCCG), equicrestal implants (3.3 x 10 mm) with bone grafts (EGG), and equicrestal implants without bone grafts (ECCG). One week following the surgical procedures, metallic prostheses were installed, and within 12 weeks the dogs were sacrificed. The blocks containing the individual implants were turned sideways, and radiographic imaging was obtained to analyze the remodeling of the buccal bone plate. In the analysis of the resulting distance between the implant shoulder and the bone crest, statistically significant differences were found in the SCTG when compared to the ECTG (P = .02) and ECCG (P = .03). For mean value comparison of the resulting linear distance between the implant surface and the buccal plate, no statistically significant difference was found among all groups (P > .05). The same result was observed in the parameter for presence or absence of tissue formation between the implant surface and buccal plate. Equicrestally placed implants, in this methodology, presented little or no loss of the buccal bone. The subcrestally positioned implants presented loss of buccal bone, even though synthetic bone graft was used. The buccal bone, however, was always coronal to the implant shoulder.

Experimental model of tooth movement in mice: A standardized protocol for studying bone remodeling under compression and tensile strains

During orthodontic tooth movement (OTM), alveolar bone is resorbed by osteoclasts in compression sites (CS) and is deposited by osteoblasts in tension sites (TS). The aim of this study was to develop a standardized OTM protocol in mice and to investigate the expression of bone resorption and deposition markers in CS and TS. An orthodontic appliance was placed in C57BL6/J mice. To define the ideal orthodontic force, the molars of the mice were subjected to forces of 0.1 N, 0.25 N, 0.35 N and 0.5 N. The expression of mediators that are involved in bone remodeling at CS and TS was analyzed using a Real-Time PCR. The data revealed that a force of 0.35 N promoted optimal OTM and osteoclast recruitment without root resorption. The levels of TNF-alpha, RANKL, MMP13 and OPG were all altered in CS and TS. Whereas TNF-a and Cathepsin K exhibited elevated levels in CS. RUNX2 and OCN levels were higher in TS. Our results suggest that 0.35 N is the ideal force for OTM in mice and has no side effects. Moreover, the expression of bone remodeling markers differed between the compression and the tension areas, potentially explaining the distinct cellular migration and differentiation patterns in each of these sites. (C) 2012 Elsevier Ltd. All rights reserved.

Influence of anatomical barriers on maxillary incisor root resorption after orthodontic treatment with premolar extractions

INTRODUCTION: Apical root resorption is a frequent and occasionally critical problem in orthodontic patients undergoing induced tooth movement. One of the factors that might influence prognosis, especially in maxillary incisors, which most frequently present resorptions, are the so-called the anatomical barriers; that is, proximity of the buccal and palatal cortical bones to the maxillary incisor roots. OBJECTIVE: The purpose of this research was to investigate whether patients with excessive vertical growth really present a small distance between the alveolar cortical bones and the maxillary incisor roots, and whether there is a correlation between this distance and the root resorption index in comparison with patients presenting horizontal growth. METHODS: The sample comprised orthodontic records of 18 patients with extraction planning of first maxillary premolars and treatment by the standard and/or preadjusted edgewise brackets. Their initial and final periapical radiographs were evaluated to determine the amount of root resorption that occurred. RESULTS: On the palatal side, patients with excessive vertical growth (Group 2 - SN-GoGn > 43º) showed a narrower alveolar bone than the horizontal growth patients (Group 1 - SN-GoGn < 29º). However, the distance between the buccal cortical bone and the central incisor root apex showed no significant difference between Groups 1 and 2; CONCLUSIONS: It was concluded that there are no correlations between the proximity of buccal cortical bone, maxillary incisor roots and the root resorption index.

Characteristics of aleveolar bone associated with physiological movement of molar in mice: a histological and histochemical study

Mouse molars undergo distal movement, during which new bone is formed at the mesial side of the tooth root whereas the preexisting bone is resorbed at the distal side of the root. However, there is little detailed information available regarding which of the bones that surround the tooth root are involved in physiological tooth movement. In the present study, we therefore aimed to investigate the precise morphological differences of the alveolar bone between the bone formation side of the tooth root, using routine histological procedures including silver impregnation, as well as by immunohistochemical analysis of alkaline phosphatase and tartrate-resistant acid phosphatase activity, and immunohistochemical analysis of the expression of the osteocyte markers dentin matrix protein 1, sclerostin, and fibroblast growth factor 23. Histochemical analysis indicated that bone formation by osteoblasts and bone resorption by osteoclasts occurred at the bone formation side and the bone resorption side, respectively. Osteocyte marker immunoreactivity of osteocytes at the surface of the bone close to the periodontal ligament differed at the bone formation and bone resorption sides. We also showed different specific features of osteocytic lacunar canalicular systems at the bone formation and bone resorption sides by using silver staining. This study suggests that the alveolar bone is different in the osteocyte nature between the bone formation side and the bone resorption side due to physiological distal movement of the mouse molar.

Prevenção da reabsorção óssea alveolar após extração dentária

Introdução: O processo alveolar é o conjunto de osso que se encontra em redor da raiz do dente. Este osso é sensível a uma variedade de fatores ambientais e fisiológicos que influenciam a sua integridade e o seu funcionamento. Como tal, a sua formação assim como a sua preservação é dependente da presença contínua do dente. A reabsorção do processo alveolar após extração dentária é uma consequência natural e fisiológica indesejável, que pode dificultar a colocação de um implante dentário na posição desejada. Com o aumento cada vez mais das demandas estéticas em medicina dentária, torna-se, portanto, necessário prevenir que a reabsorção óssea provoque este defeito na arcada dentária. Objetivos: Realizar uma revisão bibliográfica sobre as várias técnicas e materiais para preservação do rebordo alveolar, a fim de prevenir ou minimizar a reabsorção alveolar após extração dentária. Material e Métodos: A pesquisa foi realizada nas bases de dados Pubmed, B-on e Scielo, não foi aplicado nenhum limite temporal, e os critérios de inclusão foram artigos em língua inglesa e portuguesa. Num total de 164 artigos, selecionaram-se 82 estritamente relacionados com o tema. Os artigos excluídos desviavam-se do objetivo do trabalho ou eram inconclusivos. Selecionaram-se, também, capítulos do livro Clinical Periodontology and Implant Dentistry Volume 1 e 2, dos autores Niklaus P.Lang e Jan Lindhe. Desenvolvimento: De modo a compreender como o processo alveolar reabsorve, deve-se ter em conta as várias técnicas que se podem realizar para permitir uma boa quantidade de osso remanescente na arcada adequada a cada caso para uma possível reabilitação. As técnicas de preservação do osso alveolar após extração passam pela realização de técnicas cirúrgicas minimamente invasivas, estabilização do coágulo pelo princípio da cicatrização por primeira intenção usando membranas ou retalhos, preenchimento do alvéolo dentário com materiais de enxerto ou substitutos ósseos, terapias combinadas com a colocação de implantes imediatos e o recurso a células e fatores de crescimento. Conclusão: A preservação alveolar tem grande importância para uma posterior reabilitação oral com implantes com maior quantidade de osso disponível do que quando não é feita qualquer tipo de preservação. A extração das peças dentárias deve ser feita com cuidado para preservar ao máximo ou não danificar as superfícies ósseas remanescentes. É aconselhado que o encerramento da ferida seja por primeira intenção e que proporcione estabilidade ao coágulo, podendo ser usado retalhos ou mesmo membranas. O uso de enxertos ósseos tem uma importante função de proporcionar uma matriz para o coágulo se formar e promover o processo de cicatrização. O método de implante imediato, para além de ser bastante usado, tem como finalidade o conforto para o paciente de não ser submetido a uma posterior cirurgia para colocação do mesmo e, simultaneamente, mantem a estabilidade dos tecidos moles. Ainda uma técnica menos usada é com células e fatores de crescimento que proporciona uma cicatrização mais rápida e um aumento do potencial regenerativo dos tecidos.

Botulinum toxin in masticatory muscles of the adult rat induces bone loss at the condyle and alveolar regions of the mandible associated with a bone proliferation at a muscle enthesis

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Influences of age and mechanical stability on volume, microstructure, and mineralization of the fracture callus during bone healing : Is osteoclast activity the key to age-related impaired healing?

Earlier studies have shown that the influence of fixation stability on bone healing diminishes with advanced age. The goal of this study was to unravel the relationship between mechanical stimulus and age on callus competence at a tissue level. Using 3D in vitro micro-computed tomography derived metrics, 2D in vivo radiography, and histology, we investigated the influences of age and varying fixation stability on callus size, geometry, microstructure, composition, remodeling, and vascularity. Compared were four groups with a 1.5-mm osteotomy gap in the femora of Sprague–Dawley rats: Young rigid (YR), Young semirigid (YSR), Old rigid (OR), Old semirigid (OSR). Hypothesis was that calcified callus microstructure and composition is impaired due to the influence of advanced age, and these individuals would show a reduced response to fixation stabilities. Semirigid fixations resulted in a larger ΔCSA (Callus cross-sectional area) compared to rigid groups. In vitro μCT analysis at 6 weeks postmortem showed callus bridging scores in younger animals to be superior than their older counterparts (pb0.01). Younger animals showed (i) larger callus strut thickness (pb0.001), (ii) lower perforation in struts (pb0.01), and (iii) higher mineralization of callus struts (pb0.001). Callus mineralization was reduced in young animals with semirigid fracture fixation but remained unaffected in the aged group. While stability had an influence, age showed none on callus size and geometry of callus. With no differences observed in relative osteoid areas in the callus ROI, old as well as semirigid fixated animals showed a higher osteoclast count (pb0.05). Blood vessel density was reduced in animals with semirigid fixation (pb0.05). In conclusion, in vivo monitoring indicated delayed callus maturation in aged individuals. Callus bridging and callus competence (microstructure and mineralization) were impaired in individuals with an advanced age. This matched with increased bone resorption due to higher osteoclast numbers. Varying fixator configurations in older individuals did not alter the dominant effect of advanced age on callus tissue mineralization, unlike in their younger counterparts. Age-associated influences appeared independent from stability. This study illustrates the dominating role of osteoclastic activity in age-related impaired healing, while demonstrating the optimization of fixation parameters such as stiffness appeared to be less effective in influencing healing in aged individuals.

Breast cancer cells induce osteolytic bone lesions in vivo through a reduction in osteoblast activity in mice

Bone metastases are severely debilitating and have a significant impact on the quality of life of women with metastatic breast cancer. Treatment options are limited and in order to develop more targeted therapies, improved understanding of the complex mechanisms that lead to bone lesion development are warranted. Interestingly, whilst prostate-derived bone metastases are characterised by mixed or osteoblastic lesions, breast-derived bone metastases are characterised by osteolytic lesions, suggesting unique regulatory patterns. This study aimed to measure the changes in bone formation and bone resorption activity at two time-points (18 and 36 days) during development of the bone lesion following intratibial injection of MDA-MB-231 human breast cancer cells into the left tibiae of Severely Combined Immuno-Deficient (SCID) mice. The contralateral tibia was used as a control. Tibiae were extracted and processed for undecalcified histomorphometric analysis. We provide evidence that the early bone loss observed following exposure to MDA-MB-231 cells was due to a significant reduction in mineral apposition rate, rather than increased levels of bone resorption. This suggests that osteoblast activity was impaired in the presence of breast cancer cells, contrary to previous reports of osteoclast-dependent bone loss. Furthermore mRNA expression of Dickkopf Homolog 1 (DKK-1) and Noggin were confirmed in the MDA-MB-231 cell line, both of which antagonise osteoblast regulatory pathways. The observed bone loss following injection of cancer cells was due to an overall thinning of the trabecular bone struts rather than perforation of the bone tissue matrix (as measured by trabecular width and trabecular separation, respectively), suggesting an opportunity to reverse the cancer-induced bone changes. These novel insights into the mechanisms through which osteolytic bone lesions develop may be important in the development of new treatment strategies for metastatic breast cancer patients.

β-Arrestin2 regulates RANKL and Ephrins gene expression in response to bone remodeling in mice

PTH-stimulated intracellular signaling is regulated by the cytoplasmic adaptor molecule barrestin. We reported that the response of cancellous bone to intermittent PTH is reduced in b-arrestin22/2 mice and suggested that b-arrestins could influence the bone mineral balance by controlling RANKL and osteoprotegerin (OPG) gene expression. Here, we study the role of b-arrestin2 on the in vitro development and activity of bone marrow (BM) osteoclasts (OCs) and Ephrins ligand (Efn), and receptor (Eph) mRNA levels in bone in response to PTH and the changes of bone microarchitecture in wildtype (WT) and barrestin2 2/2 mice in models of bone remodeling: a low calcium diet (LoCa) and ovariectomy (OVX). The number of PTH-stimulated OCs was higher in BM cultures from b-arrestin22/2 compared with WT, because of a higher RANKL/OPG mRNA and protein ratio, without directly influencing osteoclast activity. In vivo, high PTH levels induced by LoCa led to greater changes in TRACP5b levels in b-arrestin22/2 compared with WT. LoCa caused a loss of BMD and bone microarchitecture, which was most prominent in b-arrestin22/2. PTH downregulated Efn and Eph genes in b-arrestin22/2, but not WT. After OVX, vertebral trabecular bone volume fraction and trabecular number were lower in b-arrestin22/2 compared with WT. Histomorphometry showed that OC number was higher in OVX-b-arrestin22/2 compared with WT. These results indicate that b-arrestin2 inhibits osteoclastogenesis in vitro, which resulted in decreased bone resorption in vivo by regulating RANKL/OPG production and ephrins mRNAs. As such, b-arrestins should be considered an important mechanism for the control of bone remodeling in response to PTH and estrogen deprivation.

Mice lacking β-Adrenergic receptors have increased bone mass but are not protected from deleterious skeletal effects of ovariectomy

Activation of β2-adrenergic receptors inhibits osteoblastic bone formation and enhances osteoclastic bone resorption. Whether β-blockers inhibit ovariectomy-induced bone loss and decrease fracture risk remains controversial. To further explore the role of β-adrenergic signaling in skeletal acquisition and response to estrogen deficiency, we evaluated mice lacking the three known β-adrenergic receptors (β-less). Body weight, percent fat, and bone mineral density were significantly higher in male β-less than wild-type (WT) mice, more so with increasing age. Consistent with their greater fat mass, serum leptin was significantly higher in β-less than WT mice. Mid-femoral cross-sectional area and cortical thickness were significantly higher in adult β-less than WT mice, as were femoral biomechanical properties (+28 to +49%, P < 0.01). Young male β-less had higher vertebral (1.3-fold) and distal femoral (3.5-fold) trabecular bone volume than WT (P < 0.001 for both) and lower osteoclast surface. With aging, these differences lessened, with histological evidence of increased osteoclast surface and decreased bone formation rate at the distal femur in β-less vs. WT mice. Serum tartrate-resistance alkaline phosphatase-5B was elevated in β-less compared with WT mice from 8–16 wk of age (P < 0.01). Ovariectomy inhibited bone mass gain and decreased trabecular bone volume/total volume similarly in β-less and WT mice. Altogether, these data indicate that absence of β-adrenergic signaling results in obesity and increased cortical bone mass in males but does not prevent deleterious effects of estrogen deficiency on trabecular bone microarchitecture. Our findings also suggest direct positive effects of weight and/or leptin on bone turnover and cortical bone structure, independent of adrenergic signaling.

Intermittent Fugu parathyroid hormone 1 (1–34) is an anabolic bone agent in young male rats and osteopenic ovariectomized rats

Human parathyroid hormone (hPTH) is currently the only treatment for osteoporosis that forms new bone. Previously we described a fish equivalent, Fugu parathyroid hormone 1 (fPth1) which has hPTH-like biological activity in vitro despite fPth1(1–34) sharing only 53% identity with hPTH(1–34). Here we demonstrate the in vivo actions of fPth1(1–34) on bone. In study 1, young male rats were injected intermittently for 30 days with fPth1 [30 μg–1000 μg/kg body weight (b.w.), (30fPth1–1000fPth1)] or hPTH [30 μg–100 μg/kg b.w. (30hPTH–100hPTH)]. In proximal tibiae at low doses, the fPth1 was positively correlated with trabecular bone volume/total volume (TbBV/TV) while hPTH increased TbBV/TV, trabecular thickness (TbTh) and trabecular number (TbN). 500fPth1 and 1000fPth1 increased TbBV/TV, TbTh, TbN, mineral apposition rate (MAR) and bone formation rate/bone surface (BFR/BS) with a concomitant decrease in osteoclast surface and number. In study 2 ovariectomized (OVX), osteopenic rats and sham operated (SHAM) rats were injected intermittently with 500 μg/kg b.w. of fPth1 (500fPth1) for 11 weeks. 500fPth1 treatment resulted in increased TbBV/TV (151%) and TbTh (96%) in the proximal tibiae due to increased bone formation as assessed by BFR/BS (490%) and MAR (131%). The effect was restoration of TbBV/TV to SHAM levels without any effect on bone resorption. 500fPth1 also increased TbBV/TV and TbTh in the vertebrae (L6) and cortical thickness in the mid-femora increasing bone strength at these sites. fPth1 was similarly effective in SHAM rats. Notwithstanding the low amino acid sequence homology with hPTH (1–34), we have clearly established the efficacy of fPth1 (1–34) as an anabolic bone agent.

Suggestive linkage of 2p22-25 and 11q12-13 with low bone mineral density at the lumbar spine in the Irish population

Osteoporosis is a disease characterized by low bone mineral density (BMD) and poor bone quality. Peak bone density is achieved by the third decade of life, after which bone is maintained by a balanced cycle of bone resorption and synthesis. Age-related bone loss occurs as the bone resorption phase outweighs the bone synthesis phase of bone metabolism. Heritability accounts for up to 90% of the variability in BMD. Chromosomal loci including 1p36, 2p22-25, 11q12-13, parathyroid hormone receptor type 1 (PTHR1), interleukin-6 (IL-6), interleukin 1 alpha (IL-1α) and type II collagen A1/vitamin D receptor (COL11A1/VDR) have been linked or shown suggestive linkage with BMD in other populations. To determine whether these loci predispose to low BMD in the Irish population, we investigated 24 microsatellite markers at 7 chromosomal loci by linkage studies in 175 Irish families of probands with primary low BMD (T-score ≤ -1.5). Nonparametric analysis was performed using the maximum likelihood variance estimation and traditional Haseman-Elston tests on the Mapmaker/Sibs program. Suggestive evidence of linkage was observed with lumbar spine BMD at 2p22-25 (maximum LOD score 2.76) and 11q12-13 (MLS 2.55). One region, 1p36, approached suggestive linkage with femoral neck BMD (MLS 2.17). In addition, seven markers achieved LOD scores > 1.0, D2S149, D11S1313, D11S987, D11S1314 including those encompassing the PTHR1 (D3S3559, D3S1289) for lumbar spine BMD and D2S149 for femoral neck BMD. Our data suggest that genes within a these chromosomal regions are contributing to a predisposition to low BMD in the Irish population.

ADAMs, Osteoclastogenesis and Bone Destruction in the Loosening of the Totally Replaced Hip

Total hip replacement is the golden standard treatment for severe osteoarthritis refractory for conservative treatment. Aseptic loosening and osteolysis are the major long-term complications after total hip replacement. Foreign body giant cells and osteoclasts are locally formed around aseptically loosening implants from precursor cells by cell fusion. When the foreign body response is fully developed, it mediates inflammatory and destructive host responses, such as collagen degradation. In the present study, it was hypothesized that the wear debris and foreign body inflammation are the forces driving local osteoclast formation, peri-implant bone resorption and enhanced tissue remodeling. Therefore the object was to characterize the eventual expression and the role of fusion molecules, ADAMs (an abbreviation for A Disintegrin And Metalloproteinase, ADAM9 and ADAM12) in the fusion of progenitor cells into multinuclear giant cells. For generation of such cells, activated macrophages trying to respond to foreign debris play an important role. Matured osteoclasts together with activated macrophages mediate bone destruction by secreting protons and proteinases, including matrix metalloproteinases (MMPs) and cathepsin K. Thus this study also assessed collagen degradation and its relationship to some of the key collagenolytic proteinases in the aggressive synovial membrane-like interface tissue around aseptically loosened hip replacement implants. ADAMs were found in the interface tissues of revision total hip replacement patients. Increased expression of ADAMs at both transcriptional and translational levels was found in synovial membrane-like interface tissue of revision total hip replacement (THR) samples compared with that in primary THR samples. These studies also demonstrate that multinucleate cell formation from monocytes by stimulation with macrophage-colony stimiulating factor (M-CSF) and receptor activator of nuclear factor kappa B ligand (RANKL) is characterized by time dependent changes of the proportion of ADAMs positive cells. This was observed both in the interface membrane in patients and in two different in vitro models. In addition to an already established MCS-F and RANKL driven model, a new virally (parainfluenza 2) driven model (of human salivary adenocarcinoma (HSY) cells or green monkey kidney (GMK) cells) was developed to study various fusion molecules and their role in cell fusion in general. In interface membranes, collagen was highly degraded and collagen degradation significantly correlated with the number of local cells containing collagenolytic enzymes, particularly cathepsin K. As a conclusion, fusion molecules ADAM9 and ADAM12 seem to be dynamically involved in cell-cell fusion processes and multinucleate cell formation. The highly significant correlation between collagen degradation and collagenolytic enzymes, particularly cathepsin K, indicates that the local acidity of the interface membrane in the pathologic bone and soft tissue destruction. This study provides profound knowledge about cell fusion and mechanism responsible for aseptic loosening as well as increases knowledge helpful for prevention and treatment.