Osteocytes are contained within spaces called lacunae and play a central role in bone remodelling. Administered frequently to prevent osteoporotic fractures, antiresorptive agents such as ...bisphosphonates suppress osteocyte apoptosis and may be localized within osteocyte lacunae. Bisphosphonates also reduce osteoclast viability and thereby hinder the repair of damaged tissue. Osteocyte lacunae contribute to toughening mechanisms. Following osteocyte apoptosis, the lacunar space undergoes mineralization, termed “micropetrosis”. Hypermineralized lacunae are believed to increase bone fragility. Using nanoanalytical electron microscopy with complementary spectroscopic and crystallographic experiments, postapoptotic mineralization of osteocyte lacunae in bisphosphonate-exposed human bone was investigated. We report an unprecedented presence of ∼80 nm to ∼3 μm wide, distinctly faceted, magnesium whitlockite Ca18Mg2(HPO4)2(PO4)12 crystals and consequently altered local nanomechanical properties. These findings have broad implications on the role of therapeutic agents in driving biomineralization and shed new insights into a possible relationship between bisphosphonate exposure, availability of intracellular magnesium, and pathological calcification inside lacunae.
Objective
The aim of this systematic review was to identify, review, analyze, and summarize available evidence on the accuracy of linear measurements when using maxillofacial cone beam computed ...tomography (CBCT) specifically in the field of implant dentistry.
Material and methods
The search was undertaken in April 2017 in the National Library of Medicine database (Medline) through its online site (PubMed), followed by searches in the Cochrane, EMBASE, ScienceDirect, and ProQuest Dissertation and Thesis databases. The main inclusion criterion for studies was that linear CBCT measurements were performed for quantitative assessment (e.g., height, width) of the alveolar bone at edentulous sites or measuring distances from anatomical structures related to implant dentistry. The studies should compare these values to clinical data (humans) or ex vivo and/or experimental (animal) findings from a “gold standard.”
Results
The initial search yielded 2,516 titles. In total, 22 studies were included in the final analysis. Of those, two were clinical and 20 ex vivo investigations. The major findings of the review indicate that CBCT provides cross‐sectional images that demonstrate high accuracy and reliability for bony linear measurements on cross‐sectional images related to implant treatment. A wide range of error has been reported when performing linear measurements on CBCT images, with both over‐ and underestimation of dimensions in comparison with a gold standard. A voxel size of 0.3 to 0.4 mm is adequate to provide CBCT images of acceptable diagnostic quality for implant treatment planning.
Conclusions
CBCT can be considered as an appropriate diagnostic tool for 3D preoperative planning. Nevertheless, a 2 mm safety margin to adjacent anatomic structures should be considered when using CBCT. In clinical practice, the measurement accuracy and reliability of linear measurements on CBCT images are most likely reduced through factors such as patient motion, metallic artefacts, device‐specific exposure parameters, the software used, and manual vs. automated procedures.
Aim. To evaluate, with three-dimensional analysis, the effectiveness of alveolar ridge preservation (ARP) after maxillary molar extraction in reducing alveolar bone resorption and maxillary sinus ...pneumatization when compared to unassisted socket healing. Methods. Patients were included in the study following inclusion criteria and underwent minimally traumatic maxillary molar extraction followed by ARP using synthetic nanohydroxyapatite (Fisiograft Bone, Ghimas, Italy) (test group) or unassisted socket healing (control group). Cone-beam computerized tomographies (CBCT) were performed immediately after tooth extraction (T0) and 6 months postoperatively (T1). CBCTs were superimposed by using a specific software (Amira, Thermo Fisher Scientific, USA) and the following items were analyzed in both groups: (i) postextractive maxillary sinus floor expansion in coronal direction and (ii) postextractive alveolar bone dimensional changes (both vertical and horizontal). All data were tested for normality and equality of variance and subsequently analyzed by independent samples T-test and Mann–Whitney test. Results. Thirty patients were treated by three centers and twenty-six (test n=13; control n=13) were included in the final analysis. Mean sinus pneumatization at T1 was 0.69±0.48 mm in the test group and 1.04±0.67 mm in the control group (p=0.15). Mean vertical reduction of the alveolar bone at T1 was 1.62±0.49 mm in the test group and 2.01±0.84 mm in the control group (p=0.08). Mean horizontal resorption of crestal bone at T1 was 2.73±1.68 mm in test group and 3.63±2.24 mm in control group (p=0.24). Conclusions. It could be suggested that ARP performed after maxillary molar extraction may reduce the entity of sinus pneumatization and alveolar bone resorption, compared to unassisted socket healing. This technique could decrease the necessity of advanced regenerative procedures prior to dental implant placement in posterior maxilla.
This study investigated whether osteocalcin (OCN) is present in osteoblast precursors and its relationship with initial phases of alveolar process formation. Samples of maxillae of 16-, 18-, and ...20-day-old rat embryos (E16, E18, and E20, respectively), and 05-, 10-, and 15-day-old postnatal rats (P05, P10, and P15, respectively) were fixed and embedded in paraffin or araldite. Immunohistochemistry for osterix (Osx), alkaline phosphatase (ALP), and OCN detection was performed and the number of immunolabelled cells was computed. Non-decalcified sections were subjected to the von Kossa method combined with immunohistochemistry for Osx or OCN detection. For OCN immunolocalization, samples were fixed in 0.5% glutaraldehyde/2% formaldehyde and embedded in LR White resin. The highest number of ALP- and OCN-immunolabelled cells was observed in dental follicle of E16 specimens, mainly in basal portions of dental alveolus. In corresponding regions, osteoblasts in differentiation adjacent to von Kossa-positive bone matrix exhibited Osx and OCN immunoreactivity. Ultrastructural analysis revealed OCN immunoreactive particles inside osteoblast in differentiation, and in bone matrix associated with collagen fibrils and within matrix vesicles, at early stages of alveolar process formation. Our results indicate that OCN plays a role in osteoblast differentiation and may regulate calcium/phosphate precipitation during early mineralization of the alveolar process:
Background
Alveolar ridge preservation via socket grafting (ARP‐SG) is indicated to attenuate physiologic alveolar bone resorption as a consequence of tooth extraction. However, a specific bone ...grafting material that is patently superior has not been identified yet. The aim of this randomized controlled trial was to evaluate the efficacy of a moldable alloplastic graft, Poly Lactic‐Co‐Glycolic Acid‐Coated β‐Tricalcium Phosphate (PLGA‐β‐TCP), for ARP purposes Group A compared to freeze‐dried bone allograft (FDBA) particles covered with a rapidly absorbable collagen dressing (RACD) (Group B) in function of a panel of radiographic, histomorphometric, and implant‐related outcomes.
Methods
Patients in need of extraction of a single posterior tooth (premolar or molar) and subsequent replacement with a dental implant were recruited and randomly allocated into one of the two treatment groups. Follow‐up visits took place at 1, 2, 4, 8, and 16 weeks. Cone‐beam Computed Tomography (CBCT) scans were obtained at baseline and at 16 weeks. Sites were re‐entered at 20 weeks for bone core biopsy harvesting and subsequent implant placement. After delivery of the final implant‐supported restoration, follow‐up visits were scheduled at 6 and 12 months to monitor peri‐implant tissue health and marginal bone levels using standardized intraoral periapical radiographs.
Results
A total of 45 patients were initially enrolled in the study, of whom 43 received an implant and 32 completed the study. Healing was uneventful in all sites after ARP‐SG and implant placement. No site required bone augmentation to allow for implant placement. CBCT scan analyses showed no statistically significant differences between groups in terms of reduction of horizontal width, midbuccal / midlingual height and ridge volume. Histomorphometric assessments revealed a statistically significant difference between both groups in terms of mineralized tissue formation (Group A = 27.0% ± 22.1% versus Group B = 38.2% ± 12.5%; P < 0.05). On the contrary, no significant differences were observed regarding percent of remaining bone grafting material and non‐mineralized tissue. No implant failed throughout the study period and marginal bone level change was negligible in both groups.
Conclusions
Although a higher proportion of mineralized tissue was associated with the use of FDBA+RACD compared to PLGA‐β‐TCP alone, both ARP‐SG approaches rendered comparable outcomes in terms of maintenance of alveolar bone dimensions, feasibility of implant placement, implant survival, and peri‐implant bone level stability up to 12 months post‐loading.
Previous findings indicated that the laser photobiomodulation is more effective than the control or placebo in preserving the alveolar socket. This study aimed to compare two different lasers ...regarding their effectiveness in aiding alveolar socket preservation. Twenty extraction sockets were selected then divided into two equal groups. Group A was exposed to 650 nm Diode laser, and Group B to 810 nm Diode laser following the same protocol and parameters after a standard alveolar socket preservation procedure with collagen plug. Radiographic analysis with cone beam computed tomography was done to compare the alveolar bone surface area immediately after extraction and three months post-operatively, while bone samples collected before implant drilling were histologically examined for newly formed bone evaluation and histomorphometric analysis in terms of percentage of new bone surface area, percentage of unmineralized bone and finally, immunohistochemical analysis of Osteocalcin reaction surface area as well as optical density. Radiographically, infrared (810 nm) Diode effect on alveolar bone surface area has significantly exceeded the red laser, while histologically, red (650 nm) Diode has demonstrated statistical significance regarding all parameters; newly formed bone surface area percentage, unmineralized bone area percentage and finally Osteocalcin bone marker reaction surface area percentage and optical density. Under the specified conditions and laser parameters, photobiomodulation using the 810 nm Diode got the upper hand radiographically, yet histologically, the red 650 nm Diode managed to dominate all histological parameters when both employed as an adjunct to alveolar socket preservation procedures.
Host inflammatory immune response comprises an essential element of the bone healing process, where M2 polarization allegedly contributes to a favorable healing outcome. In this context, ...immunoregulatory molecules that modulate host response, including macrophage polarization, are considered potential targets for improving bone healing. This study aims to evaluate the role of the immunoregulatory molecules VIP (Vasoactive intestinal peptide) and PACAP (Pituitary adenylate cyclase activating polypeptide), which was previously described to favor the development of the M2 phenotype, in the process of alveolar bone healing in C57Bl/6 (WT) mice. Experimental groups were submitted to tooth extraction and maintained under control conditions or treated with VIP or PACAP were evaluated by microtomographic (µCT), histomorphometric, immunohistochemical, and molecular analysis at 0, 3, 7, and 14 days to quantify tissue healing and host response indicators at the healing site. Gene expression analysis demonstrates the effectiveness of VIP or PACAP in modulating host response, evidenced by the early dominance of an M2-type response, which was paralleled by a significant increase in M2 (CD206
) in treated groups. However, despite the marked effect of M1/M2 balance in the healing sites, the histomorphometric analysis does not reveal an equivalent/corresponding modulation of the healing process. µCT reveals a slight increase in bone matrix volume and the trabecular thickness number in the PACAP group, while histomorphometric analyzes reveal a slight increase in the VIP group, both at a 14-d time-point; despite the increased expression of osteogenic factors, osteoblastic differentiation, activity, and maturation markers in both VIP and PACAP groups. Interestingly, a lower number of VIP and PACAP immunolabeled cells were observed in the treated groups, suggesting a reduction in endogenous production. In conclusion, while both VIP and PACAP treatments presented a significant immunomodulatory effect with potential for increased healing, no major changes were observed in bone healing outcome, suggesting that the signals required for bone healing under homeostatic conditions are already optimal, and additional signals do not improve an already optimal process. Further studies are required to elucidate the role of macrophage polarization in the bone healing process.
Periodontitis is an inflammation characterized by alveolar bone resorption caused by imbalance in bone homeostasis. It is known that autophagy is related to inflammation and bone metabolism. However, ...whether autophagy inhibitors could be used for periodontitis in animal models remains unknown. We investigated the role of two classical autophagy inhibitors, 3-methyladenine (3-MA) and chloroquine (CQ), on the development of rat experimental periodontitis in terms of the bone loss (micro-CT), the number of inflammatory cells (hematoxylin and eosin staining), and the osteoclastic activity (tartrate-resistant acid phosphatase staining). Expression of autophagy-related genes and nuclear factor kappa B p65 (NF-κB p65) were assessed by immunohistochemistry. Expression of Beclin-1 and microtubule-associated proteins 1A/1B light chain 3 (LC3) were analyzed by Western blot. To further observe the effect of autophagy inhibitors on osteoclasts (OCs)
in vitro
, bone marrow–derived mononuclear macrophages were used. Together, these findings indicated that topical administration of 3-MA or CQ reduced the infiltration of inflammatory cells and alveolar bone resorption in experimental periodontitis. Furthermore, 3-MA and CQ may attenuate activation of OCs by autophagy. Therefore, 3MA and CQ may have prophylactic and therapeutic potential for inflammation and alveolar bone resorption in periodontitis in the future.
Bone tissue has a significant potential for healing, which involves a significant the interplay between bone and immune cells. While fracture healing represents a useful model to investigate ...endochondral bone healing, intramembranous bone healing models are yet to be developed and characterized. In this study, a micro-computed tomography, histomorphometric and molecular (RealTimePCRarray) characterization of post tooth-extraction alveolar bone healing was performed on C57Bl/6 WT mice. After the initial clot dominance (0 h), the development of a provisional immature granulation tissue is evident (7 d), characterized by marked cell proliferation, angiogenesis and inflammatory cells infiltration; associated with peaks of growth factors (BMP-2-4-7,TGFβ1,VEGFa), cytokines (TNFα, IL-10), chemokines & receptors (CXCL12, CCL25, CCR5, CXCR4), matrix (Col1a1-2, ITGA4, VTN, MMP1a) and MSCs (CD105, CD106, OCT4, NANOG, CD34, CD146) markers expression. Granulation tissue is sequentially replaced by more mature connective tissue (14 d), characterized by inflammatory infiltrate reduction along the increased bone formation, marked expression of matrix remodeling enzymes (MMP-2-9), bone formation/maturation (RUNX2, ALP, DMP1, PHEX, SOST) markers, and chemokines & receptors associated with healing (CCL2, CCL17, CCR2). No evidences of cartilage cells or tissue were observed, strengthening the intramembranous nature of bone healing. Bone microarchitecture analysis supports the evolving healing, with total tissue and bone volumes as trabecular number and thickness showing a progressive increase over time. The extraction socket healing process is considered complete (21 d) when the dental socket is filled by trabeculae bone with well-defined medullary canals; it being the expression of mature bone markers prevalent at this period. Our data confirms the intramembranous bone healing nature of the model used, revealing parallels between the gene expression profile and the histomorphometric events and the potential participation of MCSs and immune cells in the healing process, supporting the forthcoming application of the model for the better understanding of the bone healing process.
Objective
The aim of this study was to assess the effect of different abutment configurations on peri‐implant soft and hard tissue healing.
Materials and Methods
Two‐piece dental implants, 3.5 mm in ...diameter and 8 mm in length, were placed in four beagle dogs. Two different transmucosal healing abutment configurations were randomly selected: one with a wide emergence profile (WE) (45° angulation with implant long axis) and the other with a narrow emergence profile (NE) (15° angulation with implant long axis). After four months of healing, the animals were sacrificed. Micro‐CT scans were taken for mesio‐distal analysis; subsequently, the biopsies were prepared for bucco–lingual histometric analyses. Several measurements were taken using the following reference points: marginal mucosal level (MML), apical barrier epithelium (aBE), implant shoulder (IS), marginal bone crest (BC), and first bone‐to‐implant contact (fBIC).
Results
In the micro‐CT analysis, the distance from IS‐fBIC was 1.11 ± 0.66 mm for WE and 0.12 ± 0.21 mm for NE (p = 0.004). The IS‐BC of WE was −0.54 ± 0.80 mm, whereas NE presented 0.76 ± 0.48 mm (p = 0.002). The histometric analysis showed that both groups presented comparable dimensions of peri‐implant biologic width (p > 0.05). However, in the distance from IS to BC, the WE showed a mean distance of −0.66 ± 0.78 mm while NE was 0.06 ± 0.42 mm (p = 0.039); the IS to fBIC was 0.89 ± 0.68 mm for WE while NE was 0.30 ± 0.30 mm (p = 0.041).
Conclusion
The design of the transmucosal component can influence the establishment of the peri‐implant biologic width. The flat and wide emergence profile induced an apical displacement of the peri‐implant biologic width and more bone loss.
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