Alveolar bone grafting in association with polyostotic fibrous dysplasia and bisphosphonate-induced abnormal bone turnover in a bilateral cleft lip and palate patient: a case report

A case is presented of extensive alveolar bone grafting in a patient with bilateral cleft lip and palate and polyostotic fibrous dysplasia. The patient previously underwent bisphosphonate therapy. Because of an abnormal and often decreased bone turnover caused by the fibrous dysplasia and the bisphosphonate therapy, bone grafting in such a patient poses several potential difficulties. In addition, the histomorphometric analysis of the bone grafts showed markedly decreased bone turnover. However, alveolar bone grafting using the iliac crest was performed successfully. Sufficient occlusion was achieved by postoperative low-loading orthodontic treatment.

Human alveolar echinococcosis after fox population increase, Switzerland

We analyzed databases spanning 50 years, which included retrospective alveolar echinococcosis (AE) case finding studies and databases of the 3 major centers for treatment of AE in Switzerland. A total of 494 cases were recorded. Annual incidence of AE per 100,000 population increased from 0.12-0.15 during 1956-1992 and a mean of 0.10 during 1993-2000 to a mean of 0.26 during 2001-2005. Because the clinical stage of the disease did not change between observation periods, this increase cannot be explained by improved diagnosis. Swiss hunting statistics suggested that the fox population increased 4-fold from 1980 through 1995 and has persisted at these higher levels. Because the period between infection and development of clinical disease is long, the increase in the fox population and high Echinococcus multilocularis prevalence rates in foxes in rural and urban areas may have resulted in an emerging epidemic of AE 10-15 years later.

Long-term follow-up of metabolic activity in human alveolar echinococcosis using FDG-PET

AIM: [(18)F]fluoro-deoxyglucose positron-emission-tomography (FDG-PET) detects metabolic activity in alveolar echinococcosis (AE). The slow changes in metabolic and morphological characteristics require long-term follow-up of patients. This is the first study to evaluate metabolic activity over may years, hereby assessing the utility of FDG-PET for the evaluation of disease progression and response to treatment. PATIENTS, METHODS: 15 patients received a follow-up FDG-PET combined with computed tomography (integrated PET/CT) with a median of 6.5 years after the first PET in 1999. Number and location of enhanced metabolic activity in the area of AE lesions was determined. Quantification of intensity of metabolic activity was assessed by calculation of mean standardized uptake values. RESULTS: AE lesions in 11/15 patients had been metabolically inactive initially, but only two showed permanent inactivity over the course of 81 months. Interestingly, in two patients metabolic activity was newly detected after 80 and 82 months. Benzimidazole treatment was intermittently discontinued in seven cases. Persisting activity at FDG-PET demanded continued benzimidazole treatment in four patients. Neither treatment duration, lesional size, calcifications nor regressive changes correlated with metabolic activity. CONCLUSION: Treatment responses are heterogeneous and vary from progressive disease despite treatment to long-term inactive disease with discontinued treatment. Lack of metabolic activity indicates suppressed parasite activity and is not equivalent to parasite death. However, metabolic activity may remain suppressed for years, allowing for temporary treatment discontinuation. Relapses are reliably detected with PET and restarting benzimidazole treatment prevents parasite expansion.

In vitro characterization of immune-related properties of human fetal bone cells for potential tissue engineering applications

We describe herein some immunological properties of human fetal bone cells recently tested for bone tissue-engineering applications. Adult mesenchymal stem cells (MSCs) and osteoblasts were included in the study for comparison. Surface markers involved in bone metabolism and immune recognition were analyzed using flow cytometry before and after differentiation or treatment with cytokines. Immunomodulatory properties were studied on activated peripheral blood mononuclear cells (PBMCs). The immuno-profile of fetal bone cells was further investigated at the gene expression level. Fetal bone cells and adult MSCs were positive for Stro-1, alkaline phosphatase, CD10, CD44, CD54, and beta2-microglobulin, but human leukocyte antigen (HLA)-I and CD80 were less present than on adult osteoblasts. All cells were negative for HLA-II. Treatment with recombinant human interferon gamma increased the presence of HLA-I in adult cells much more than in fetal cells. In the presence of activated PBMCs, fetal cells had antiproliferative effects, although with patterns not always comparable with those of adult MSCs and osteoblasts. Because of the immunological profile, and with their more-differentiated phenotype than of stem cells, fetal bone cells present an interesting potential for allogeneic cell source in tissue-engineering applications.

Morphology–elasticity relationships using decreasing fabric information of human trabecular bone from three major anatomical locations

With improving clinical CT scanning technology, the accuracy of CT-based finite element (FE) models of the human skeleton may be ameliorated by an enhanced description of apparent level bone mechanical properties. Micro-finite element (μFE) modeling can be used to study the apparent elastic behavior of human cancellous bone. In this study, samples from the femur, radius and vertebral body were investigated to evaluate the predictive power of morphology–elasticity relationships and to compare them across different anatomical regions. μFE models of 701 trabecular bone cubes with a side length of 5.3 mm were analyzed using kinematic boundary conditions. Based on the FE results, four morphology–elasticity models using bone volume fraction as well as full, limited or no fabric information were calibrated for each anatomical region. The 5 parameter Zysset–Curnier model using full fabric information showed excellent predictive power with coefficients of determination ( r2adj ) of 0.98, 0.95 and 0.94 of the femur, radius and vertebra data, respectively, with mean total norm errors between 14 and 20%. A constant orthotropy model and a constant transverse isotropy model, where the elastic anisotropy is defined by the model parameters, yielded coefficients of determination between 0.90 and 0.98 with total norm errors between 16 and 25%. Neglecting fabric information and using an isotropic model led to r2adj between 0.73 and 0.92 with total norm errors between 38 and 49%. A comparison of the model regressions revealed minor but significant (p<0.01) differences for the fabric–elasticity model parameters calibrated for the different anatomical regions. The proposed models and identified parameters can be used in future studies to compute the apparent elastic properties of human cancellous bone for homogenized FE models.

In vitro-activity of oily calcium hydroxide suspension on microorganisms as well as on human alveolar osteoblasts and periodontal ligament fibroblasts.

BACKGROUND Findings from animal and human studies have indicated that an oily calcium hydroxide suspension (OCHS) may improve early wound healing in the treatment of periodontitis. Calcium hydroxide as the main component is well known for its antimicrobial activity, however at present the effect of OCHS on the influence of periodontal wound healing/regeneration is still very limited. The purpose of this in vitro study was to investigate the effect of OCHS on periodontopathogenic bacteria as well as on the attachment and proliferation of osteoblasts and periodontal ligament fibroblasts. METHODS Human alveolar osteoblasts (HAO) and periodontal ligament (PDL) fibroblasts were cultured on 3 concentrations of OCHS (2.5, 5 and 7.5 mg). Adhesion and proliferation were counted up to 48 h and mineralization was assayed after 1 and 2 weeks. Furthermore potential growth inhibitory activity on microorganisms associated with periodontal disease (e.g. Porphyromonas gingivalis, Tannerella forsythia, Aggregatibacter actinomycetemcomitans) as well as the influence of periodontopathogens and OCHS on the HAO and PDL fibroblasts counts were determined. RESULTS More than a 2-fold increase in adherent HAO cells was observed at 4 h following application of OCHS when compared to the control group (p = 0.007 for 2.5 mg). Proliferation of HAO cells at 48 h was stimulated by moderate concentrations (2.5 mg; 5 mg) of OCHS (each p < 0.001), whereas a high concentration (7.5 mg) of OCHS was inhibitory (p = 0.009). Mineralization was observed only for HAO cells treated with OCHS. OCHS did not exert any positive effect on attachment or proliferation of PDL fibroblasts. Although OCHS did not have an antibacterial effect, it did positively influence attachment and proliferation of HAO cells and PDL fibroblasts in the presence of periodontopathogens. CONCLUSIONS The present data suggests that OCHS promotes osteoblast attachment, proliferation and mineralization in a concentration-dependent manner and results are maintained in the presence of periodontal pathogens.

Alveolar bone regeneration in response to local application of calcitriol in vitamin D deficient rats

AIM Vitamin D deficiency is considered to diminish bone regeneration. Yet, raising the serum levels takes months. A topic application of the active vitamin D metabolite, calcitriol, may be an effective approach. Thus, it becomes important to know the effect of vitamin D deficiency and local application on alveolar bone regeneration. MATERIAL AND METHODS Sixty rats were divided into three groups; two vitamin depletion groups and a control group. Identical single defects (2 mm diameter) were created in the maxilla and mandible treated with calcitriol soaked collagen in one deficiency group while in the other two groups not. Histomorphometric analysis and micro CTs were performed after 1 and 3 weeks. Serum levels of 25(OH)D3 and PTH were determined. RESULTS Bone formation rate significantly increased within the observation period in all groups. Bone regeneration was higher in the maxilla than in the mandible. However, bone regeneration was lower in the control group compared to vitamin depletion groups, with no significant effects by local administration of calcitriol (micro CT mandible p = 0.003, maxilla p < 0.001; histomorphometry maxilla p = 0.035, mandible p = 0.18). CONCLUSION Vitamin D deficiency not necessarily impairs bone regeneration in the rat jaw and a single local calcitriol application does not enhance healing.

Mechanism of silica -induced apoptosis in human alveolar macrophages

The mechanisms involved in the development of pulmonary silicosis have not been well defined, however most current evidence implicates a central role for alveolar macrophages in this process. We propose that the fibrotic potential of a particulate depends upon its ability to cause apoptosis in alveolar macrophage (AM). The overall goal of this study was to determine the mechanism of silica-induced apoptosis of AM. Human AM were treated with fibrogenic, poorly fibrogenic and nonfibrogenic model particulates, such as, silica, amorphous silica and titanium dioxide, respectively (equal surface area). Treatment with silica resulted in apoptosis in human AM as observed by morphology, DNA fragmentation and Cell Death ELISA assays. In contrast, amorphous silica and titanium dioxide demonstrated no significant apoptotic potential. To elucidate the possible mechanism by which silica causes apoptosis, we investigated the role of the scavenger receptor (SR) in silica-induced apoptosis. Cells were pretreated with and without SR ligand binding inhibitors, polyinosinic acid (Poly I), fucoidan and high density lipoprotein (HDL), prior to silica treatment. Pretreatment with Poly I and fucoidan resulted in significant inhibition of silica-induced apoptosis suggesting that silica-induced AM apoptosis is mediated via the SR. Further, we examined the involvement of interleukin converting enzyme (ICE) family of proteases in silica-mediated apoptosis. Silica activated ICE, Ich-1L, cpp32 beta and cleavage of PARP. Taken together, these results suggested that (1) fibrogenic particulates, such as, silica caused apoptosis of alveolar macrophages, (2) this apoptotic potential of fibrogenic particulates may be a critical factor in initiating an inflammatory response resulting in fibrosis, (3) silica-induced apoptosis of alveolar macrophages may be due to the interaction of silica particulates with the SR, and (4) silica-induced apoptosis involves the activation of the ICE family of proteases. An understanding of the molecular events involved in fibrogenic particulate-induced apoptosis may provide a useful insight into the mechanism involved in particulate-induced fibrosis. ^

Molecular Characterization of Three Canine Models of Human Rare Bone Diseases: Caffey, van den Ende-Gupta, and Raine Syndromes.

One to two percent of all children are born with a developmental disorder requiring pediatric hospital admissions. For many such syndromes, the molecular pathogenesis remains poorly characterized. Parallel developmental disorders in other species could provide complementary models for human rare diseases by uncovering new candidate genes, improving the understanding of the molecular mechanisms and opening possibilities for therapeutic trials. We performed various experiments, e.g. combined genome-wide association and next generation sequencing, to investigate the clinico-pathological features and genetic causes of three developmental syndromes in dogs, including craniomandibular osteopathy (CMO), a previously undescribed skeletal syndrome, and dental hypomineralization, for which we identified pathogenic variants in the canine SLC37A2 (truncating splicing enhancer variant), SCARF2 (truncating 2-bp deletion) and FAM20C (missense variant) genes, respectively. CMO is a clinical equivalent to an infantile cortical hyperostosis (Caffey disease), for which SLC37A2 is a new candidate gene. SLC37A2 is a poorly characterized member of a glucose-phosphate transporter family without previous disease associations. It is expressed in many tissues, including cells of the macrophage lineage, e.g. osteoclasts, and suggests a disease mechanism, in which an impaired glucose homeostasis in osteoclasts compromises their function in the developing bone, leading to hyperostosis. Mutations in SCARF2 and FAM20C have been associated with the human van den Ende-Gupta and Raine syndromes that include numerous features similar to the affected dogs. Given the growing interest in the molecular characterization and treatment of human rare diseases, our study presents three novel physiologically relevant models for further research and therapy approaches, while providing the molecular identity for the canine conditions.

Treatment With a Growth Factor-Protein Mixture Inhibits Formation of Mineralized Nodules in Osteogenic Cell Cultures Grown on Titanium

Despite wide clinical application, the efficacy of platelet-rich plasma (PRP) for repairing bone defects and enhancing osseointegration of metal implants is still subject of debate. This study aimed to evaluate the effects of a well-defined PRP-like mixture containing platelet-derived growth factor-BB, transforming growth factor (TGF)-beta 1, TGF-beta 2, albumin, fibronectin, and thrombospondin [growth factors (GFs) + proteins] on the development of the osteogenic phenotype on titanium (Ti) in vitro. Human alveolar bone-derived osteoblastic cells were subcultured on Ti discs and exposed during the first 7 days to osteogenic medium supplemented with GFs + proteins and to osteogenic medium alone thereafter up to 14 days. Control cultures were exposed to only osteogenic medium. Dose-response experiments were carried out using rat primary calvarial cells exposed to GFs + proteins and 1:10 or 1:100 dilutions of the mixture. Treated human-derived cell cultures exhibited a significantly higher number of cycling cells at days 1 and 4 and of total cells at days 4 and 7, significantly reduced alkaline phosphatase (ALP) activity at days 4, 7, and 10, and no Alizarin red-stained areas (calcium deposits) at day 14, indicating an impairment in osteoblast differentiation. Although the 1:10 and 1:100 dilutions of the mixture restored the proliferative activity of rat-derived osteogenic cells to control levels and promoted a significant increase in ALP activity at day 10 compared with GFs + proteins, mineralized nodule formation was only observed with the 1:100 dilution (similar to 50% of the control). These results showed that a PRP-like protein mixture inhibits development of the osteogenic phenotype in both human and rat osteoblastic cell cultures grown on Ti. (J Histochem Cytochem 57:265-276, 2009)