Discontinuation of simvastatin leads to a rebound phenomenon and results in immediate peri-implant bone loss.
ABSTRACT: Although administration of simvastatin has been reported to promote bone formation, the effect of short-term simvastatin administration is not well known. Following implant installation, 10-week-old male Wistar rats (n?=?24) were divided into two groups randomly. The experimental group received 10?mg/kg of simvastatin daily for seven days. Then simvastatin administration was discontinued, and the animals were observed up to 28?days. Animals in the control group underwent the same procedure but received saline instead of simvastatin. All animals were analyzed by micro-computed tomography. Samples at days 14 and 21 were subjected to histological analyses. After seven days of simvastatin administration, more new bone formation around the implant was observed in the simvastatin group compared with the control group. Seven days after simvastatin discontinuation, however, the amount of peri-implant trabecular bone began to decrease. Results from morphometric analysis also showed a reduction in new bone area after day 7, which was lowest at day 14. These results were confirmed by histological analyses. In contrast, both the peri-implant trabecular bone and new bone area were maintained in the control group. Short-term administration of simvastatin may affect implant stability owing to a rebound phenomenon and an immediate loss of peri-implant bone.
Project description:Although osteoporotic bone, with low bone mass and deteriorated bone architecture, provides a less favorable mechanical environment than healthy bone for implant fixation, there is no general agreement on the impact of osteoporosis on peri-implant bone (re)modeling, which is ultimately responsible for the long term stability of the bone-implant system. Here, we inserted an implant in a mouse model mimicking estrogen deficiency-induced bone loss and we monitored with longitudinal in vivo micro-computed tomography the spatio-temporal changes in bone (re)modeling and architecture, considering the separate contributions of trabecular, endocortical and periosteal surfaces. Specifically, 12 week-old C57BL/6J mice underwent OVX/SHM surgery; 9 weeks after we inserted special metal-ceramics implants into the 6th caudal vertebra and we measured bone response with in vivo micro-CT weekly for the following 6 weeks. Our results indicated that ovariectomized mice showed a reduced ability to increase the thickness of the cortical shell close to the implant because of impaired peri-implant bone formation, especially at the periosteal surface. Moreover, we observed that healthy mice had a significantly higher loss of trabecular bone far from the implant than estrogen depleted animals. Such behavior suggests that, in healthy mice, the substantial increase in peri-implant bone formation which rapidly thickened the cortex to secure the implant may raise bone resorption elsewhere and, specifically, in the trabecular network of the same bone but far from the implant. Considering the already deteriorated bone structure of estrogen depleted mice, further bone loss seemed to be hindered. The obtained knowledge on the dynamic response of diseased bone following implant insertion should provide useful guidelines to develop advanced treatments for osteoporotic fracture fixation based on local and selective manipulation of bone turnover in the peri-implant region.
Project description:Osseointegration is the key to implant stability and occlusal support. Biomechanical response and remodeling of peri-implant bone occurs under impact loading. Sclerostin participates in bone formation and resorption through Wnt and RANKL pathways. However the mechanism of microdamage and expression of sclerostin in peri-implant bone under impact load is still unclear. In present study, specific impact forces were applied to the implants with favorable osseointegration in rabbits. The microdamage of peri-implant bone and the expression of sclerostin, ?-catenin and RANKL during the process of bone damage and remodeling were investigated by micro-CT, histology, immunofluorescence and RT-qPCR analysis. Interface separation and trabecular fracture were found histologically, which were consistent with micro-CT analyses. Throughout remodeling, bone resorption was observed during the first 14 days after impact, and osseointegration and normal trabecular structure were found by 28?d. The expression of sclerostin and RANKL increased after impact and reached a maximum by 14?d, then decreased gradually to normal levels by 28?d. And ?-catenin expression was opposite. Results indicated that sclerostin may involve in the peri-implant bone damage caused by impact and remodeling through Wnt/?-catenin and RANKL/RANK pathways. It will provide a new insight in the diagnosis and treatment for patients suffering impact.
Project description:Cone-beam computed tomography (CBCT) has been recently used to analyse trabecular bone structure around dental implants. To validate the use of CBCT for three-dimensional (3D) peri-implant trabecular bone morphometry by comparing it to two-dimensional (2D) histology, 36 alveolar bone samples (with implants n=27 vs. without implants n=9) from six mongrel dogs, were scanned ex vivo using a high-resolution (80 µm) CBCT. After scanning, all samples were decalcified and then sectioned into thin histological sections (∼6 μm) to obtain high contrast 2D images. By using CTAn imaging software, bone morphometric parameters including trabecular number (Tb.N), thickness (Tb.Th), separation (Tb.Sp) and bone volume fraction (BV/TV) were examined on both CBCT and corresponding histological images. Higher Tb.Th and Tb.Sp, lower BV/TV and Tb.N were found on CBCT images (P<0.001). Both measurements on the peri-implant trabecular bone structure showed moderate to high correlation (r=0.65-0.85). The Bland-Altman plots showed strongest agreement for Tb.Th followed by Tb.Sp, Tb.N and BV/TV, regardless of the presence of implants. The current findings support the assumption that peri-implant trabecular bone structures based on high-resolution CBCT measurements are representative for the underlying histological bone characteristics, indicating a potential clinical diagnostic use of CBCT-based peri-implant bone morphometric characterisation.
Project description:Metallic implants are frequently used in medicine to support and replace degenerated tissues. Implant loosening due to particle exposure remains a major cause for revision arthroplasty. The exact role of metal debris in sterile peri-implant inflammation is controversial, as it remains unclear whether and how metals chemically alter and potentially accumulate behind an insulating peri-implant membrane, in the adjacent bone and bone marrow (BM). An intensively focused and bright synchrotron X-ray beam allows for spatially resolving the multi-elemental composition of peri-implant tissues from patients undergoing revision surgery. In peri-implant BM, particulate cobalt (Co) is exclusively co-localized with chromium (Cr), non-particulate Cr accumulates in the BM matrix. Particles consisting of Co and Cr contain less Co than bulk alloy, which indicates a pronounced dissolution capacity. Particulate titanium (Ti) is abundant in the BM and analyzed Ti nanoparticles predominantly consist of titanium dioxide in the anatase crystal phase. Co and Cr but not Ti integrate into peri-implant bone trabeculae. The characteristic of Cr to accumulate in the intertrabecular matrix and trabecular bone is reproducible in a human 3D in vitro model. This study illustrates the importance of updating the view on long-term consequences of biomaterial usage and reveals toxicokinetics within highly sensitive organs.
Project description:Multiple case reports using recombinant human bone morphogenetic protein-2 (rhBMP-2) have reported complications. However, the local adverse effects of rhBMP-2 application are not well documented. In this report we show that, in addition to promoting lumbar spinal fusion through potent osteogenic effects, rhBMP-2 augmentation promotes local cyst-like osteolytic formations in sheep trabecular bones that have undergone anterior lumbar interbody fusion. Three months after operation, conventional computed tomography showed that the trabecular bones of the rhBMP-2 application groups could fuse, whereas no fusion was observed in the control group. Micro-computed tomography analysis revealed that the core implant area's bone volume fraction and bone mineral density increased proportionately with rhBMP-2 dose. Multiple cyst-like bone voids were observed in peri-implant areas when using rhBMP-2 applications, and these sites showed significant bone mineral density decreases in relation to the unaffected regions. Biomechanically, these areas decreased in strength by 32% in comparison with noncystic areas. Histologically, rhBMP-2-affected void sites had an increased amount of fatty marrow, thinner trabecular bones, and significantly more adiponectin- and cathepsin K-positive cells. Despite promoting successful fusion, rhBMP-2 use in clinical applications may result in local adverse structural alterations and compromised biomechanical changes to the bone.
Project description:This report is the second part of the previously published study on the impact of light/chemical hardening technology and a newly formulated composite graft material for crestal augmentation during immediate implant placement.A total of 48 implants were placed into the sockets of the mesial roots of freshly extracted mandibular premolar teeth in three minipigs. Crestal areas and intrabony spaces were randomly augmented with light-hardened graft materials including a composite graft consisting of polymethylmethacrylate, polyhydroxylethylmethacrylate, and calcium hydroxide (PPCH) plus polyanhydride (PA); PPCH graft; and PA graft, or left untreated. Distal sockets not receiving implants and the sockets of first molars (n = 60) were randomly treated with one of the graft materials or left empty. In addition, two molar sockets were treated with the original PPCH graft material. Quantitative microcomputed tomography (micro-CT) was used to assess alveolar bone structure and tissue compositions. Histologic evaluations included descriptive histology to assess the peri-implant wound healing, as well as histomorphometric measurements to determine bone-to-implant contact (BIC).Both trabecular and cortical bone measurements by micro-CT did not reveal any significant differences among the groups. Sites augmented with PPCH+PA resulted in significantly greater BIC surface than PPCH alone and no-graft-treated implants (P <0.05) histologically. Stained ground sections showed complete bone formation between bone and implant surface in the PPCH+PA group, whereas sites without augmentation showed large gaps between bone and implant surfaces, indicating a slower bone apposition and less BIC surface compared to all other groups. Similar to implant sections, all materials showed positive outcome on trabecular and cortical bone formation in extraction sockets with an intact crestal cortical bone.Histologic evaluations supported the previous findings on implant stability and function and confirmed that PPCH+PA provides a greater BIC with a well-organized implant-bone interface and is useful in crestal augmentation during immediate implant placement.
Project description:BACKGROUNDS:This study aimed to evaluate the microstructural changes in the peri-implant bone in patients with short implants in terms of implant survival status by using fractal analysis measurements. RESULTS:Dental panoramic radiographs (DPRs) of 67 patients were examined and included in this study. Fractal analysis and measurement of the crown-implant ratio were performed with ImageJ. The fractal analysis measurement was performed on the DPRs obtained at preoperative (FD0) and in the follow-up periods (after 2 ± 2?weeks (FD1), 2?months ± 2?weeks (FD2), 6?months ± 2?weeks (FD3), and 12?months + (FD4)). A p value < 0.05 was considered statistically significant. Power analyses were conducted for the test results that did not reject null hypothesis. A significant difference was found in the FD1 and FD2 values between the implant survival groups (p < 0.001 and p = 0.023, respectively). The mean FD1 and FD2 values of the success group were significantly higher than those of the failure group. CONCLUSIONS:Fractal analysis is a useful method to measure the trabecular microstructure of bone in non-standardized dental radiographs. The present study has a low power to reject the null hypothesis because of the low number of cases of implant failure. Therefore, further study with a large sample size is warranted. In clinical practice, the survival of implants may be predicted by analyzing fractal dimension of the surrounding trabecular bone of the implants.
Project description:In patients presenting mucositis, effective sub-gingival debridement is crucial to prevent peri-implantitis. The aim of this randomized study was to assess the three-month (T1) effects of a locally delivered liquid desiccant agent with molecular hygroscopic properties, in association with manual debridement, at sites with peri-implant mucositis. Twenty-three patients presenting at least one implant with no radiographically detectable bone loss, a pocket probing depth (PPD) ? 4 mm, and bleeding on probing (BOP), were included. At baseline (T0), patients were randomly assigned to receive the aforementioned desiccant agent before debridement (Test-Group), or a Chlorhexidine 1% disinfectant gel after debridement (Control-Group). Treatments were repeated after seven and 14 days. Peri-implant soft tissue assessment [PPD, BOP, Modified Bleeding Index (mBI), Visible Plaque Index (VPI), and Modified Plaque Index (mPLI)] and microbial sampling were performed at T0 and T1. At T1 the Test-Group presented significantly greater reductions for BOP, mBI, VPI, and mPLI. Concerning the deepest sites of the treated implants, both groups showed statistically significant reductions for BOP and mBI between T0 and T1. Furthermore, the Test-Group exhibited a significant decrease in anaerobic bacteria. Despite these valid outcomes, a complete resolution of the inflammatory conditions was not achieved by any of the groups.
Project description:The aim of this study was to compare the release of bone markers during osseointegration of immediately loaded and nonloaded implants. Forty patients who were indicated for rehabilitation with dental implants randomly received either implant and prosthesis placement within 72 hours (group IM) or implant insertion and no prosthesis placement (group NL). Peri-implant crevicular fluid was collected immediately after implant insertion and 7, 15, 30, 60, 90, and 120 days after surgery and levels of osteoprotegerin, transforming growth factors, osteocalcin, osteopontin, and parathyroid hormone were evaluated using Luminex assay. Bleeding index and peri-implantar sulcus depth were also evaluated. The data were compared using statistical tests (? = 5%). No statistical difference was found regarding demographic and clinical parameters (p > .05). Transforming growth factors, osteoprotegerin, osteopontin, and parathyroid hormone presented an earlier release peak in group IM than in NL group (p < .05). Osteocalcin achieved higher levels in group IM versus group NL between 7 and 30 days of evaluation (p < .05). It may be concluded that earlier loading positively modulates bone mediators release around immediately loaded implants when compared with nonloaded dental implants.
Project description:BACKGROUND:The present study was to determine the effect of local anti-RANKL antibody administration in the presence or absence of microRNA-146a on ligature-induced peri-implant bone resorption, and the potential role of TLR2/4 signaling in such effect. RESULTS:Titanium implants were placed in the left maxilla alveolar bone 6?weeks after extraction of first and second molars in C57/BL6 wild-type (WT) and TLR2-/- TLR4-/- (TLR2/4 KO) mice. Silk ligatures were tied around the implants 4?weeks after implantation. Anti-RANKL antibody (500??g/mL) with or without microRNA 146a (miR-146a) (100?nM) was injected into palatal gingiva around implant on days 3, 6, and 9 during 2 weeks of ligation period. Bone resorption around the implants was assessed by 2D imaging using area measurement and 3D imaging using micro-computed tomography (?CT). Real-time quantitative PCR (RT-qPCR) was used to determine the peri-implant gingival mRNA expression levels of pro-inflammatory cytokines (TNF-?) and osteoclastogenesis-related cytokines (RANKL). In both WT and TLR2/4 KO mice, the bone resorption around implants was significantly increased in the ligation only group when compared to the non-ligation group, but TLR2/4 KO mice showed significantly less bone loss compared to WT mice after ligation. As expected, gingival injection of anti-RANKL antibody significantly reduced bone loss compared with the ligation only group in both WT and TLR2/4 KO mice. Moreover, injection of miR-146a in addition to anti-RANKL antibody significantly enhanced the inhibition of bone loss in WT mice but not in TLR2/4 KO mice. Gingival mRNA expressions of RANKL were significantly reduced by anti-RANKL antibody treatment in both WT and TLR2/4 KO mice but were not affected by the additional miR-146a treatment. Gingival mRNA expression of TNF-? was significantly reduced by miR-146a treatment in WT mice but not in TLR2/4 KO mice. The number of gingival inflammatory cell infiltration and peri-implant TRAP-positive cell formation was significantly reduced by the additional miR-146a treatment in WT mice but not in TLR2/4 KO mice. CONCLUSIONS:This study suggests that anti-inflammatory miR-146a enhance anti-RANKL-induced inhibition of peri-implant bone resorption through the regulation of TLR2/4 signaling and inhibition of TNF-? expression.