Biomechanical loading modulates proinflammatory and bone resorptive mediators in bacterial-stimulated PDL cells.

The present study aimed to evaluate in vitro whether biomechanical loading modulates proinflammatory and bone remodeling mediators production by periodontal ligament (PDL) cells in the presence of bacterial challenge. Cells were seeded on BioFlex culture plates and exposed to Fusobacterium nucleatum ATCC 25586 and/or cyclic tensile strain (CTS) of low (CTSL) and high (CTSH) magnitudes for 1 and 3 days. Synthesis of cyclooxygenase-2 (COX2) and prostaglandin E2 (PGE2) was evaluated by ELISA. Gene expression and protein secretion of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-B ligand (RANKL) were evaluated by quantitative RT-PCR and ELISA, respectively. F. nucleatum increased the production of COX2 and PGE2, which was further increased by CTS. F. nucleatum-induced increase of PGE2 synthesis was significantly (P < 0.05) increased when CTSH was applied at 1 and 3 days. In addition, CTSH inhibited the F. nucleatum-induced upregulation of OPG at 1 and 3 days, thereby increasing the RANKL/OPG ratio. OPG and RANKL mRNA results correlated with the protein results. In summary, our findings provide original evidence that CTS can enhance bacterial-induced syntheses of molecules associated with inflammation and bone resorption by PDL cells. Therefore, biomechanical, such as orthodontic or occlusal, loading may enhance the bacterial-induced inflammation and destruction in periodontitis.

Clinical outcomes following regenerative therapy of non-contained intrabony defects using a deproteinized bovine bone mineral combined with either enamel matrix derivative or collagen membrane

BACKGROUND The purpose of this study is to compare clinical outcomes in the treatment of deep non-contained intrabony defects (i.e., with ≥70% 1-wall component and a residual 2- to 3-wall component in the most apical part) using deproteinized bovine bone mineral (DBBM) combined with either enamel matrix protein derivative (EMD) or collagen membrane (CM). METHODS Forty patients with multiple intrabony defects were enrolled. Only one non-contained defect per patient with an intrabony depth ≥3 mm located in the interproximal area of single- and multirooted teeth was randomly assigned to the treatment with either EMD + DBBM (test: n = 20) or CM + DBBM (control: n = 20). At baseline and after 12 months, clinical parameters including probing depth (PD) and clinical attachment level (CAL) were recorded. The primary outcome variable was the change in CAL between baseline and 12 months. RESULTS At baseline, the intrabony component of the defects amounted to 6.1 ± 1.9 mm for EMD + DBBM and 6.0 ± 1.9 mm for CM + DBBM sites (P = 0.81). The mean CAL gain at sites treated with EMD + DBBM was not statistically significantly different (P = 0.82) compared with CM + DBBM (3.8 ± 1.5 versus 3.7 ± 1.2 mm). No statistically significant difference (P = 0.62) was observed comparing the frequency of CAL gain ≥4 mm between EMD + DBBM (60%) and CM + DBBM (50%) or comparing the frequency of residual PD ≥6 mm between EMD + DBBM (5%) and CM + DBBM (15%) (P = 0.21). CONCLUSION Within the limitations of the present study, regenerative therapy using either EMD + DBBM or CM + DBBM yielded comparable clinical outcomes in deep non-contained intrabony defects after 12 months.

Crestal bone changes at teeth and implants in periodontally healthy and periodontally compromised patients. A 10-year comparative case-series study

BACKGROUND Limited data exist on the longitudinal crestal bone changes around teeth compared with implants in partially edentulous patients. This study sought to compare the 10-year radiographic crestal bone changes (bone level [BL]) around teeth and implants in periodontally compromised (PCPs) and periodontally healthy (PHPs) patients. METHODS A total of 120 patients were evaluated for the radiographic crestal BL around dental implants and adjacent teeth at time of implant crown insertion and at the 10-year follow-up. Sixty patients had a previous history of periodontitis (PCPs), and the remaining 60 were PHPs. In each category (PCP and PHP), two different implant systems were used. The mean BL change at the implant and at the adjacent tooth at the interproximal area was calculated by subtracting the radiographic crestal BL at the time of crown cementation from the radiographic crestal BL at the 10-year follow-up. RESULTS At 10 years after therapy, the survival rate ranged from 80% to 95% for subgroups for implants, whereas it was 100% for the adjacent teeth. In all eight different patient categories evaluated, teeth demonstrated a significantly more stable radiographic BL compared with adjacent dental implants (teeth BL, 0.44 ± 0.23 mm; implant BL, 2.28 ± 0.72 mm; P <0.05). Radiographic BL changes around teeth seemed not to be influenced by the presence or absence of advanced bone loss (≥3 mm) at the adjacent implants. CONCLUSIONS Natural teeth yielded better long-term results with respect to survival rate and marginal BL changes compared with dental implants. Moreover, these findings also extend to teeth with an initial reduced periodontal attachment level, provided adequate periodontal treatment and maintenance are performed. As a consequence, the decision of tooth extraction attributable to periodontal reasons in favor of a dental implant should be carefully considered in partially edentulous patients.

Enamel matrix derivative in combination with bone grafts: A review of the literature.

OBJECTIVE Over 15 years have passed since an enamel matrix derivative (EMD) was introduced as a biologic agent capable of periodontal regeneration. Histologic and controlled clinical studies have provided evidence for periodontal regeneration and substantial clinical improvements following its use. The purpose of this review article was to perform a systematic review comparing the eff ect of EMD when used alone or in combination with various types of bone grafting material. DATA SOURCES A literature search was conducted on several medical databases including Medline, EMBASE, LILACS, and CENTRAL. For study inclusion, all studies that used EMD in combination with a bone graft were included. In the initial search, a total of 820 articles were found, 71 of which were selected for this review article. Studies were divided into in vitro, in vivo, and clinical studies. The clinical studies were subdivided into four subgroups to determine the eff ect of EMD in combination with autogenous bone, allografts, xenografts, and alloplasts. RESULTS The analysis from the present study demonstrates that while EMD in combination with certain bone grafts is able to improve the regeneration of periodontal intrabony and furcation defects, direct evidence supporting the combination approach is still missing. CONCLUSION Further controlled clinical trials are required to explain the large variability that exists amongst the conducted studies.

Is a grooved collar implant design superior to a machined design regarding bone level alteration? An observational pilot study.

OBJECTIVE This retrospective observational pilot study examined differences in peri-implant bone level changes (ΔIBL) between two similar implant types differing only in the surface texture of the neck. The hypothesis tested was that ΔIBL would be greater with machined-neck implants than with groovedneck implants. METHOD AND MATERIALS 40 patients were enrolled; n = 20 implants with machined (group 1) and n = 20 implants with a rough, grooved neck (group 2), all placed in the posterior mandible. Radiographs were obtained after loading (at 3 to 9 months) and at 12 to 18 months after implant insertion. Case number calculation with respect to ΔIBL was conducted. Groups were compared using a Brunner-Langer model, the Mann-Whitney test, the Wilcoxon signed rank test, and linear model analysis. RESULTS After the 12- to 18-month observation period, mean ΔIBL was -1.11 ± 0.92 mm in group 1 and -1.25 ± 1.23 mm in group 2. ΔIBL depended significantly on time (P < .001), but not on group. In both groups, mean marginal ΔIBL was significantly less than -1.5 mm. Only insertion depth had a significant influence on the amount of periimplant bone loss (P = .013). Case number estimate testing for a difference between group 1 and 2 with a power of 90% revealed a sample size per group of 1,032 subjects. CONCLUSION ΔIBL values indicated that both implant designs fulfilled implant success criteria, and the modification of implant neck texture had no significant influence on ΔIBL.

Radiographic bone level changes of implant-supported restorations in edentulous and partially dentate patients: 5-year results.

PURPOSE To evaluate and compare crestal bone level changes and peri-implant status of implant-supported reconstructions in edentulous and partially dentate patients after a minimum of 5 years of loading. MATERIALS AND METHODS All patients who received a self-tapping implant with a microstructured surface during the years 2003 and 2004 at the Department of Prosthodontics, University of Bern, were included in this study. The implant restorations comprised fixed and removable prostheses for partially and completely edentulous patients. Radiographs were taken immediately after surgery, at impression making, and 1 and 5 years after loading. Crestal bone level (BIC) was measured from the implant shoulder to the first bone contact, and changes were calculated over time (ΔBIC). The associations between pocket depth, bleeding on probing (BOP), and ΔBIC were assessed. RESULTS Sixty-one implants were placed in 20 patients (mean age, 62 ± 7 years). At the 5-year follow-up, 19 patients with 58 implants were available. Implant survival was 98.4% (one early failure; one patient died). The average ΔBIC between surgery and 5-year follow-up was 1.5 ± 0.9 mm and 1.1 ± 0.6 mm for edentulous and partially dentate patients, respectively. Most bone resorption (50%, 0.7 mm) occurred during the first 3 months (osseointegration) and within the first year of loading (21%, 0.3 mm). Mean annual bone loss during the 5 years of loading was < 0.12 mm. Mean pocket depth was 2.6 ± 0.7 mm. Seventeen percent of the implant sites displayed BOP; the frequency was significantly higher in women. None of the variables were significantly associated with crestal bone loss. CONCLUSION Crestal bone loss after 5 years was within the normal range, without a significant difference between edentulous and partially dentate patients. In the short term, this implant system can be used successfully for various prosthetic indications.

Saliva suppresses osteoclastogenesis in murine bone marrow cultures.

Saliva can reach mineralized surfaces in the oral cavity; however, the relationship between saliva and bone resorption is unclear. Herein, we examined whether saliva affects the process of osteoclastogenesis in vitro. We used murine bone marrow cultures to study osteoclast formation. The addition of fresh sterile saliva eliminated the formation of multinucleated cells that stained positive for tartrate-resistant acid phosphatase (TRAP). In line with the histochemical staining, saliva substantially reduced gene expression of cathepsin K, calcitonin receptor, and TRAP. Addition of saliva led to considerably decreased gene expression of receptor activator of nuclear factor kappa-B (RANK) and, to a lesser extent, that of c-fms. The respective master regulators of osteoclastogenesis (c-fos and NFATc1) and the downstream cell fusion genes (DC-STAMP and Atp6v0d2) showed decreased expression after the addition of saliva. Among the costimulatory molecules for osteoclastogenesis, only OSCAR showed decreased expression. In contrast, CD40, CD80, and CD86-all costimulatory molecules of phagocytic cells-were increasingly expressed with saliva. The phagocytic capacity of the cells was confirmed by latex bead ingestion. Based on these in vitro results, it can be concluded that saliva suppresses osteoclastogenesis and leads to the development of a phagocytic cell phenotype.

Cytotoxic CD8+ T cells stimulate hematopoietic progenitors by promoting cytokine release from bone marrow mesenchymal stromal cells.

Cytotoxic CD8(+) T cells (CTLs) play a major role in host defense against intracellular pathogens, but a complete clearance of pathogens and return to homeostasis requires the regulated interplay of the innate and acquired immune systems. Here, we show that interferon γ (IFNγ) secreted by effector CTLs stimulates hematopoiesis at the level of early multipotent hematopoietic progenitor cells and induces myeloid differentiation. IFNγ did not primarily affect hematopoietic stem or progenitor cells directly. Instead, it promoted the release of hematopoietic cytokines, including interleukin 6 from bone marrow mesenchymal stromal cells (MSCs) in the hematopoietic stem cell niche, which in turn reduced the expression of the transcription factors Runx-1 and Cebpα in early hematopoietic progenitor cells and increased myeloid differentiation. Therefore, our study indicates that, during an acute viral infection, CTLs indirectly modulate early multipotent hematopoietic progenitors via MSCs in order to trigger the temporary activation of emergency myelopoiesis and promote clearance of the infection.

Intraoperative Mechanical Measurement of Bone Quality With the DensiProbe.

Reduced bone stock can result in fractures that mostly occur in the spine, distal radius, and proximal femur. In case of operative treatment, osteoporosis is associated with an increased failure rate. To estimate implant anchorage, mechanical methods seem to be promising to measure bone strength intraoperatively. It has been shown that the mechanical peak torque correlates with the local bone mineral density and screw failure load in hip, hindfoot, humerus, and spine in vitro. One device to measure mechanical peak torque is the DensiProbe (AO Research Institute, Davos, Switzerland). The device has shown its effectiveness in mechanical peak torque measurement in mechanical testing setups for the use in hip, hindfoot, and spine. In all studies, the correlation of mechanical torque measurement and local bone mineral density and screw failure load could be shown. It allows the surgeon to judge local bone strength intraoperatively directly at the region of interest and gives valuable information if additional augmentation is needed. We summarize methods of this new technique, its advantages and limitations, and give an overview of actual and possible future applications.

The molecular signature of the stroma response in prostate cancer-induced osteoblastic bone metastasis highlights expansion of hematopoietic and prostate epithelial stem cell niches

The reciprocal interaction between cancer cells and the tissue-specific stroma is critical for primary and metastatic tumor growth progression. Prostate cancer cells colonize preferentially bone (osteotropism), where they alter the physiological balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption, and elicit prevalently an osteoblastic response (osteoinduction). The molecular cues provided by osteoblasts for the survival and growth of bone metastatic prostate cancer cells are largely unknown. We exploited the sufficient divergence between human and mouse RNA sequences together with redefinition of highly species-specific gene arrays by computer-aided and experimental exclusion of cross-hybridizing oligonucleotide probes. This strategy allowed the dissection of the stroma (mouse) from the cancer cell (human) transcriptome in bone metastasis xenograft models of human osteoinductive prostate cancer cells (VCaP and C4-2B). As a result, we generated the osteoblastic bone metastasis-associated stroma transcriptome (OB-BMST). Subtraction of genes shared by inflammation, wound healing and desmoplastic responses, and by the tissue type-independent stroma responses to a variety of non-osteotropic and osteotropic primary cancers generated a curated gene signature ("Core" OB-BMST) putatively representing the bone marrow/bone-specific stroma response to prostate cancer-induced, osteoblastic bone metastasis. The expression pattern of three representative Core OB-BMST genes (PTN, EPHA3 and FSCN1) seems to confirm the bone specificity of this response. A robust induction of genes involved in osteogenesis and angiogenesis dominates both the OB-BMST and Core OB-BMST. This translates in an amplification of hematopoietic and, remarkably, prostate epithelial stem cell niche components that may function as a self-reinforcing bone metastatic niche providing a growth support specific for osteoinductive prostate cancer cells. The induction of this combinatorial stem cell niche is a novel mechanism that may also explain cancer cell osteotropism and local interference with hematopoiesis (myelophthisis). Accordingly, these stem cell niche components may represent innovative therapeutic targets and/or serum biomarkers in osteoblastic bone metastasis.

Increased bone mineral density at the hypoxia prone site of the juxta-articular metacarpal bone in patients with limited systemic sclerosis: a cross-sectional study

OBJECTIVES Low levels of oxygen has been shown to be involved in the induction of osteogenesis, particularly in bone repair. It is unknown whether hypoxia leads to osteogenesis at the hypoxia prone skeletal sites in limited systemic sclerosis. This study determined the total and trabecular volumetric bone mineral density (vBMD) at the hypoxia prone site of the juxta-articular metacarpal bone. METHODS In this cross-sectional study, female patients with limited systemic sclerosis were included and compared to healthy controls. Peripheral quantitative computed tomography was used to measure cross-sectional area, total vBMD, and trabecular vBMD at the radius, the tibia and the third metacarpal bone. Disease severity was assessed by the modified Rodnan Skin Score. RESULTS Twenty consecutive patients were included in the sclerosis group and 20 in the control group. Mean age was 60 years (range 52-68 years), and mean disease duration was 45 months (range 4-156 months). Age, height, and weight were comparable between the groups. The mean modified Rodnan Skin Score was 1.78 (range 0 to 8). The sclerosis group showed both higher total and trabecular vBMD at the distal metacarpal bone (p=0.05 and 0.04, respectively). vBMD of the tibia and radius did not differ in both groups. CONCLUSIONS vBMD at the juxta-articular metacarpal bone in patients with limited systemic sclerosis is increased, possibly due to an alteration in local bone metabolism and hypoxia induced local osteogenesis.

Comparative effects of teriparatide and ibandronate on spine bone mineral density (BMD) and microarchitecture (TBS) in postmenopausal women with osteoporosis: a 2-year open-label study

UNLABELLED Treatment effects over 2 years of teriparatide vs. ibandronate in postmenopausal women with osteoporosis were compared using lumbar spine bone mineral density (BMD) and trabecular bone score (TBS). Teriparatide induced larger increases in BMD and TBS compared to ibandronate, suggesting a more pronounced effect on bone microarchitecture of the bone anabolic drug. INTRODUCTION The trabecular bone score (TBS) is an index of bone microarchitecture, independent of bone mineral density (BMD), calculated from anteroposterior spine dual X-ray absorptiometry (DXA) scans. The potential role of TBS for monitoring treatment response with bone-active substances is not established. The aim of this study was to compare the effects of recombinant human 1-34 parathyroid hormone (teriparatide) and the bisphosphonate ibandronate (IBN), on lumbar spine (LS) BMD and TBS in postmenopausal women with osteoporosis. METHODS Two patient groups with matched age, body mass index (BMI), and baseline LS BMD, treated with either daily subcutaneous teriparatide (N = 65) or quarterly intravenous IBN (N = 122) during 2 years and with available LS BMD measurements at baseline and 2 years after treatment initiation were compared. RESULTS Baseline characteristics (overall mean ± SD) were similar between groups in terms of age 67.9 ± 7.4 years, body mass index 23.8 ± 3.8 kg/m(2), BMD L1-L4 0.741 ± 0.100 g/cm(2), and TBS 1.208 ± 0.100. Over 24 months, teriparatide induced a significantly larger increase in LS BMD and TBS than IBN (+7.6 % ± 6.3 vs. +2.9 % ± 3.3 and +4.3 % ± 6.6 vs. +0.3 % ± 4.1, respectively; P < 0.0001 for both). LS BMD and TBS were only weakly correlated at baseline (r (2) = 0.04) with no correlation between the changes in BMD and TBS over 24 months. CONCLUSIONS In postmenopausal women with osteoporosis, a 2-year treatment with teriparatide led to a significantly larger increase in LS BMD and TBS than IBN, suggesting that teriparatide had more pronounced effects on bone microarchitecture than IBN.