HLA-DR alleles are associated with IDDM, but not with impaired neutrophil chemotaxis in IDDM.

Insulin-dependent diabetes mellitus (IDDM) is a risk factor for periodontitis. Depressed neutrophil chemotaxis has been demonstrated in IDDM and in early-onset periodontitis (EOP). HLA-DR antigens are associated with both IDDM and periodontitis. This investigation sought to determine an association of HLA-DR3, -DR4, and -DR53 with impaired neutrophil chemotaxis in an IDDM sample. The neutrophil chemotaxis index of 41 diabetics and 27 controls was determined by a modified Boyden chamber method, and certain class II HLA genotypes were determined by polymerase chain-reaction amplification of genomic DNA by means of sequence-specific primers (PCR-SSP). The mean chemotaxis index of the diabetics was significantly less than that of the controls (p < or = 0.02). HLA-DR3 (p < or = 0.002), -DR4 (p < 0.003), and -DR53 (p < or = 0.001) were associated with IDDM. Neutrophil chemotaxis and glucose metabolism were not significantly correlated. None of the HLA-DR alleles was associated with impaired neutrophil chemotaxis. Therefore, the neutrophil chemotaxis defect of IDDM appears to be independent of these HLA-DR-associated genes.

Cell and fiber attachment to demineralized cementum from normal root surfaces.

The purpose of this study was to assess connective tissue and epithelial responses to cementum (from normal human root surfaces covered by periodontal ligament) after surface demineralization with citric acid. Each rectangular specimen had a face of cementum and an opposite surface composed of pulpal dentin. One half of the specimens were treated with citric acid (experimental group), while the remainder served as untreated control specimens. Specimens were implanted vertically into incisional wounds on the dorsal surface of rats with one end of the implant protruding through the skin. Four specimens in each group were available for examination 1, 3, 5, and 10 days after implantation. Histologic and histometric analyses of the implants included counts of adhering cells, evaluation of attached connective tissue fiber density and diameter, and assessment of epithelial migration. At day 1, a distinct lighter staining zone was present on the surface of both cementum and dentin in the experimental group which corresponded to a zone of surface demineralization produced by the acid treatment. Histometric comparisons between experimental and control groups at 10 days showed a greater number of cells attached to demineralized cementum surfaces. Also, a connective tissue fiber attachment system had developed on these experimental surfaces, but which differed morphologically from periodontal ligament fiber attachment to normal cementum. It was concluded that citric acid treatment can surface demineralize cementum from normal roots, and that the surface demineralization of this cementum facilitated a cell and fiber attachment to the cementum surface.

Cell and fiber attachment to demineralized dentin from periodontitis-affected root surfaces.

This study assessed connective tissue and epithelial responses to dentin specimens obtained from periodontitis-affected roots of human teeth after surface demineralization. Rectangular dentin specimens with opposite faces of root and pulpal dentin were prepared from beneath root surfaces covered by sheets of calculus. One half of the specimens were treated with citric acid, pH 1, for 3 minutes, while the remainder served as untreated controls. Specimens were implanted vertically into incisional wounds on the dorsal surface of rats with one end of the implant protruding through the skin. Four specimens in each group were available 1, 3, 5 and 10 days after implantation. Histologic and histometric analyses included counts of adhering cells, evaluation of attached connective tissue fiber density and diameter, and assessment of epithelial migration. Analyses within each group comparing root and pulpal surfaces showed no differences between any of the parameters. Comparisons between experimental and control groups showed that demineralized surfaces had a greater number of cells attached, fiber attachment occurred and epithelial downgrowth was inhibited. Surface demineralization of dentin from periodontitis-affected roots predisposed toward a connective tissue attachment.

Cell and fiber attachment to demineralized dentin from normal root surfaces.

The study assessed connective tissue and epithelial responses to dentin specimens (obtained from normal roots of human teeth) after surface demineralization. Rectangular dental specimens with opposite faces of root and pulpal dentin were prepared from beneath root surfaces covered by periodontal ligament. One-half of the specimens were treated with citric acid, pH 1, for 3 minutes, while the remainder served as untreated control specimens. Specimens were implanted vertically into incisional wounds on the dorsal surface of rats with one end of the implant protruding through the skin. Four specimens in each group were available 1, 3, 5 and 10 days after implantation. Histologic and histometric analyses included counts of adhering cells, evaluation of connective tissue fiber relationships and assessment of epithelial migration. Analyses within each group comparing root and pulpal surfaces showed no differences between any of the parameters. Comparisons between experimental and control groups showed that demineralized surfaces had a greater number of cells attached, fiber attachment occurred and epithelial downgrowth was inhibited. The fiber attachment to experimental specimens differed morphologically from fiber attachment to normal root surfaces: the number of fibers attached per unit length and the diameter of attached fibers were significantly less on experimental specimens. Demineralized specimens at 10 days had a distinct eosinophilic surface zone. Surface demineralization of dentin predisposed toward a cell and fiber attachment system which inhibited migration of epithelium.

Binding, uptake, and release of nicotine by human gingival fibroblasts.

Previous studies of the effects of nicotine on fibroblasts have reported an altered morphology and attachment of fibroblasts to substrates and disturbances in protein synthesis and secretion. This altered functional and attachment response may be associated with changes in the cell membrane resulting from binding of the nicotine, or to disturbances in cell metabolism as a result of high intracellular levels of nicotine. The purpose of the present study, therefore, was to 1) determine whether gingival fibroblasts bound nicotine and if any binding observed was specific or non-specific in nature; 2) determine whether gingival fibroblasts internalized nicotine, and if so, at what rate; 3) determine whether gingival fibroblasts also released nicotine back into the extracellular environment; and 4) if gingival fibroblasts release nicotine intact or as a metabolite. Cultures of gingival fibroblasts were prepared from gingival connective tissue biopsies. Binding was evaluated at 4 degrees C using a mixture of 3H-nicotine and unlabeled nicotine. Specific binding was calculated as the difference between 3H-nicotine bound in the presence and absence of unlabeled nicotine. The cells bound 1.44 (+/- 0.42) pmols/10(6) cells in the presence of unlabeled nicotine and 1.66 (+/- 0.55) pmols/10(6) cells in the absence of unlabeled nicotine. The difference was not significant. Uptake of nicotine was measured at 37 degrees C after treating cells with 3H-nicotine for time periods up to 4 hours. Uptake in pmols/10(6) cells was 4.90 (+/- 0.34) at 15 minutes, 8.30 (+/- 0.75) at 30 minutes, 12.28 (+/- 2.62) at 1 hour and 26.31 (+/- 1.15) at 4 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Initial wound healing attachments to demineralized dentin.

This report describes the initial in vivo wound healing response of connective tissue components and cells to demineralized and nondemineralized dentin surfaces. Rectangular dentin specimens were prepared from beneath root surfaces covered by periodontal ligament. One group of six specimens were treated with citric acid, while another six specimens served as untreated controls. Specimens were implanted vertically into the skin of rats such that one end of the implant protruded above the skin. After one day, the implants were removed, and the dentin surface-connective tissue interface was examined using scanning electron microscopic methods. The surface of the nondemineralized dentin implants had the morphological characteristics of a surface smear layer. Cells that were present on these nondemineralized surfaces were rounded in shape with few processes or extensions to the dentin surface or to other cells. The surfaces of the demineralized dentin implants were fibrillar in appearance and were usually covered by a layer that had many globular and fibrillar structures attached. Cells that were present on these demineralized surfaces exhibited marked bipolarity with distinct attachments to the dentin surface. Cell processes often extended into the openings of demineralized dentin tubules. It was concluded that an established cellular and connective tissue response to demineralized dentin occurred within the first 24 hours of wound healing, and that this response differed markedly from that associated with nondermineralized dentin surfaces.

The production of a root surface smear layer by instrumentation and its removal by citric acid.

The purpose of this study was to characterize, using the scanning electron microscope, the nature of root surfaces denuded by (1) root planing alone or (2) root planing plus citric acid treatment. Six teeth were extracted from three squirrel monkeys, and the coronal half of the root surface was planed to remove attached periodontal ligament fibers and cementum. Citric acid, pH 1, was topically applied to the denuded surfaces of 3 teeth. The surface of only root-planed specimens had an irregular surface which corresponded to a smear layer. Root surfaces that had received acid treatment after root planing exhibited funnel-shaped orifices of dentinal tubules, and intertubular zones with a fibrillar, mat-like morphology. The implications of the different root-surface characteristics are discussed.

Transmission electron microscopic and high voltage electron microscopic observations of the bone and osteocyte activity adjacent to unloaded dental implants placed in dogs.

The purpose of this report is to describe ultrastructural observations of the bone and associated tissues supporting 24 unloaded endosteal dental implants placed in mongrel dogs (canis familiaris). The following 3 specific areas of the supporting tissues were targeted: 1) the osteocyte populations; 2) the mineralized collagen fiber matrix of the bone; and 3) an electron dense interfacial deposit. To investigate these areas, transmission electron microscopy and high voltage electron microscopic (HVEM) protocols were emphasized. HVEM permitted stereologic observations. Further, all observations were obtained from undecalcified tissues obtained from animals with commercially available implants placed into the mandible. From the study we observed a mineralization pattern of the implant supporting bone that was similar to those events occurring naturally within the mandibular bone. Osteocyte morphology was similar whether the osteocytes were found well below the implant interface or close to the interface. Osteocytes within lacunae were routinely found close to the implant interface, often extending cellular processes through canaliculi to the bone-implant interface. At the interface, an electron dense deposit approximately 50 nm in thickness was often observed. In interfacial regions, densely mineralized collagen fibers were observed running primarily parallel to the implant surface. This dense mineralized tissue was separated from the interface by a mineralized, but finely fibrillar matrix of approximately 200 nm in thickness.

Osteoblast activity at the dental implant-bone interface: transmission electron microscopic and high voltage electron microscopic observations.

The purpose of this report is to present transmission electron microscopic and high voltage transmission electron microscopic (HVEM) observations of a longitudinal investigation examining the activities of osteoblasts and associated tissues apposing titanium and alumina oxide ceramic endosteal dental implants. The HVEM permitted 3-dimensional stereologic observations. All observations were obtained from undecalcified interfacial tissues from this in vivo experimental dog model using commercially available implants placed into the mandible. Two similar implants were placed in both sides of the mandible, with implants in 12 of the 18 dogs supporting fixed bridges for either 6 or 12 months. From the study, we observed that a mineralized matrix exists in direct apposition to the implant. Since bone does not interface the entire length of the implant, other interfacial zones were found to exist which consisted of unmineralized tissues. In such zones, we observed that osteoblasts were routinely found directly at the implant interface to the mandibular bone. These interfacial tissues included unmineralized collagen fibers, proteinaceous material, a finely fibrillar matrix, and the osteoblasts. This study has reinforced the concept that the oral tissue-dental implant interface is a dynamic zone consisting of remodeling activities of the osseous cells and extracellular matrices.

Interleukin-1beta regulation of adhesion molecules on human gingival and periodontal ligament fibroblasts.

BACKGROUND: Adhesion molecules have been implicated in the pathogenesis of rheumatoid arthritis and may also play a role in the pathogenesis of periodontal disease by promoting the recruitment and retention of leukocytes in gingival tissue. METHODS: The aim of the present study was to evaluate the capacity of interleukin-1beta (IL-1beta) to regulate adhesion molecule expression on clinically healthy human gingival (HGF) and periodontal ligament (PDL) fibroblasts. The HGF (n = 6) and PDL (n = 3) fibroblasts were treated with 1.0 ng/ml of IL-1beta for 24 hours and then incubated with primary intercellular adhesion molecule-1 (ICAM-1) and vascular cellular adhesion molecule-1 (VCAM-1) antibodies followed by FITC-conjugated secondary antibodies. The expression of ICAM-1 and VCAM-1 was measured by immunofluorescence flow cytometry. RESULTS: The levels of ICAM-1 expression in IL-1beta treated HGF and PDL fibroblasts were statistically significant (P < or = 0.05) compared to normal untreated controls using log-transformed data and 3-way analysis of variance. Both cells expressed VCAM-1 after IL-1beta treatment, but the levels were not statistically different from controls. CONCLUSIONS: This study demonstrated that IL-1beta upregulated ICAM-1 expression in both HGF and PDL fibroblasts. Even though the level of VCAM-1 was not statistically different from both HGF and PDL fibroblasts treated with IL-1beta compared to controls, both cells do express the VCAM-1 molecules. These results suggest that ICAM-1 and VCAM-1 might be involved in the pathogenesis of periodontal disease.

Multi-center comparative evaluation of subgingivally delivered sanguinarine and doxycycline in the treatment of periodontitis. I. Study design, procedures, and management.

The design and conduct of a 9-month multi-center clinical trial to evaluate the safety and efficacy of subgingivally delivered 5% sanguinarium chloride (SC) and 10% doxycycline hyclate (DH) from a biodegradable drug delivery system in the treatment of adult periodontitis is described. The 3-group randomized study of 180 adults with moderate to severe periodontitis was a modified double-blind parallel design. One group received DH, one group received SC, and the other group received the vehicle control (VC). Patients selected had two quadrants with a minimum of four periodontal pockets > or = 5 mm in depth with two sites > or = 7 mm. All qualifying sites exhibited bleeding on gentle probing. Qualifying sites were treated at baseline and again at 4 months. Clinical response was assessed by measuring attachment level, probing depth, and bleeding on probing at monthly examinations at qualifying sites and the entire dentition. The plaque index was measured monthly to verify oral hygiene status. The parallel design afforded the opportunity to distinguish between treatment effectiveness of SC, DH, and VC independent of possible crossover effects. Also the effectiveness of oral hygiene in untreated sites of the mouth could be evaluated. Finally, treatment effects in moderate (5 to 6 mm) and deep (> or = 7 mm) pockets in both treated and untreated sites could be compared. The design was capable of simulating a periodontal practice maintenance program and assessing the response according to maintenance and treatment history. Study management procedures that emphasized center examiner and therapist training and adherence to protocol and procedures to reduce variability are described.

Multi-center comparative evaluation of subgingivally delivered sanguinarine and doxycycline in the treatment of periodontitis. II. Clinical results.

The clinical safety and effectiveness of a subgingivally delivered biodegradable drug delivery system containing either 10% doxycycline hyclate (DH), 5% sanguinarium chloride (SC) or no agent (VC) was evaluated in a 9-month multi-center trial. The study was a randomized parallel design with 180 patients who demonstrated moderate to severe periodontitis. All patients had at least two quadrants with a minimum of four qualifying pockets > or = 5 mm that bled on probing. Two of the qualifying pockets were required to be > or = 7 mm. At baseline and at 4 months all qualified sites were treated with the test article administered via syringe. Probing depth reduction (PDR), attachment level gain (ALG), bleeding on probing reduction (BOP), and plaque index were determined monthly. Analysis of efficacy data from the 173 efficacy-evaluable patients indicated that all treatments gave significant positive clinical changes from baseline at all subsequent timepoints. DH was superior to SC and VC in PDR at all timepoints (P < or = 0.01 to 0.001) with a maximum reduction of 2.0 mm at 5 months. For ALG, DH was superior to VC at months 2, 3, 4, 5, 6, 8, and 9 (P < or = 0.04 to 0.002) and superior to SC at months 5, 6, 7, 8, and 9 (P < or = 0.01 to 0.001) with a maximum ALG of 1.2 mm at 6 months. For BOP reduction, DH was superior to VC at all time points (P < or = 0.05) and to SC at months 3, 5, 6, 8, and 9 (P < or = 0.03). For DH, the maximum ALG in deep (> or = 7 mm) pockets was 1.7 mm and PDR 2.9 mm compared to 0.8 mm and 1.6 mm, respectively for moderate (5 to 6 mm) pockets. Test articles were applied without anesthesia and no serious adverse events occurred in the trial. The results of this study indicate that 10% doxycycline hyclate delivered in a biodegradable delivery system is an effective means of reducing the clinical signs of adult periodontitis and exhibits a benign safety profile.

Comparison of morphological measurements extracted from digitized dental radiographs with lumbar and femoral bone mineral density measurements in postmenopausal women.

BACKGROUND: We set out to determine whether morphologic measurements extracted from digitized images of bite-wing radiographs correlated with lumbar and femoral bone mineral density (BMD) measurements in 45 postmenopausal women who had no or only mild periodontal disease (no probing depths >5 mm). METHODS: Lumbar spine and femoral BMDs were determined by dual-energy x-ray absorptiometry. Vertical bite-wing radiographs were taken and digitized. Crestal and apical regions of interest (ROIs) were drawn on the digital images of the maxillary and mandibular alveolar bone on the patient's right and left sides. For each patient, a single morphologic measurement was made for each of 8 ROIs. Correlation analysis was performed to determine the strengths of the relationships between the morphologic measurements made at the 8 locations and between these morphologic measurements and BMD measurements. RESULTS: The correlations (r) between the morphologic operator (MO) measurements and lumbar spine and femoral BMDs were weak (mean r = 0.02, range = 0.32 to -0.26) and not statistically significant, with no clear trends discernible. Correlations between MO measurements made at the 8 alveolar sites were also weak (mean r = 0.05, range = 0.35 to -0.38) and not statistically significant. CONCLUSIONS: The MO measurements used in this study were weakly correlated with lumbar spine and femoral BMDs, with no clear trends discernible in this population of postmenopausal women with no or mild periodontal disease.

Alveolar bone height and postcranial bone mineral density: negative effects of cigarette smoking and parity.

BACKGROUND: Our objective was to test the association between cemento-enamel junction, alveolar-crest distance (CEJ-AC, as measured on digitized vertical bite-wing radiographs) and postcranial bone mineral density (BMD) relative to clinical, dietary, and demographic variables. METHODS: Data were collected in a cross-sectional study of 134 postmenopausal women. CEJ-AC distances were determined from digitized vertical bite-wing radiographs. Lumbar spine and proximal femur BMDs were determined from dual-energy x-ray absorptiometric scans. Correlation analysis and Student t tests were used to identify those variables most associated with CEJ-AC distance. The selected variables were modeled with a backward stepwise regression analysis, with CEJ-AC distance as the dependent variable. RESULTS: Parity (number of pregnancies to term), cigarette smoking, and the interaction of lateral spine BMD with cigarette smoking were independent predictors of CEJ-AC distance (P < or =0.05). Statistical models containing these variables accounted for 19% of the variation in CEJ-AC distances. CONCLUSIONS: CEJ-AC distance in postmenopausal women is the result of a complicated interaction of many effects, including but not limited to, parity, cigarette smoking, and skeletal BMD.

Two multi-center studies evaluating locally delivered doxycycline hyclate, placebo control, oral hygiene, and scaling and root planing in the treatment of periodontitis.

BACKGROUND: The clinical efficacy and safety of doxycycline hyclate (8.5% w/w) delivered subgingivally in a biodegradable polymer (DH) was compared to placebo control (VC), oral hygiene (OH), and scaling and root planing (SRP) in 2 multi-center studies. METHODS: Each study entered 411 patients who demonstrated moderate to severe periodontitis. Patients had 2 or more quadrants each with a minimum of 4 qualifying pockets > or =5 mm that bled on probing. At least 2 of the pockets were > or =7 mm. Treatment with DH, VC, OH, or SRP was provided at baseline and again at month 4. Clinical parameters were recorded monthly. RESULTS: DH and SRP resulted in nearly identical clinical changes over time in both studies. Mean 9 month clinical attachment level gain (ALG) was 0.8 mm for the DH group and 0.7 mm for the SRP group in Study 1, and 0.8 mm (DH) and 0.9 mm (SRP) in Study 2. Mean probing depth (PD) reduction was 1.1 mm for the DH group and 0.9 mm for the SRP group in Study 1 and 1.3 mm for both groups in Study 2. Frequency distributions showed an ALG > or =2 mm in 29% of DH sites versus 27% of SRP sites in Study 1 and 31% of DH sites versus 34% of SRP sites in Study 2. PD reductions > or =2 mm were seen in 32% of DH sites versus 31% of SRP sites in Study 1 and 41% of DH sites versus 43% of SRP sites in Study 2. Comparisons between DH, VC, and OH treatment groups showed DH treatment to be statistically superior to VC and OH. Safety data demonstrated a benign safety profile with use of the DH product. CONCLUSIONS: Results of this trial demonstrate that treatment of periodontitis with subgingivally delivered doxycycline in a biodegradable polymer is equally effective as scaling and root planing and superior in effect to placebo control and oral hygiene in reducing the clinical signs of adult periodontitis over a 9-month period. This represents positive changes resulting from the use of subgingivally applied doxycycline as scaling and root planing was not limited regarding time of the procedure or use of local anesthesia.

The effect of locally delivered controlled-release doxycycline or scaling and root planing on periodontal maintenance patients over 9 months.

BACKGROUND: This research report evaluates clinical changes resulting from local delivery of doxycycline hyclate (DH) or traditional scaling and root planing (SRP) in a group of patients undergoing supportive periodontal therapy (SPT). METHODS: In all, 141 patients received either DH (67) or SRP (74) treatment in sites > or =5 mm on one-half of their dentition at baseline and month 4. RESULTS: Clinical results were determined at month 9. Baseline mean probing depth recordings were similar between the two groups (DH = 5.9 mm; SRP = 5.9 mm). Mean month 9 results showed similar clinical results for attachment level gain (DH 0.7 mm; SRP 0.8 mm) and probing depth reduction (DH 1.3 mm; SRP 1.1 mm). Percentage of sites showing > or =2 mm attachment level gain at month 9 was 24.7% in the DH group and 21.2% in the SRP group. Thirty-nine percent (39%) of DH sites and 38% of SRP sites showed > or =2 mm probing depth reduction. When treated sides of the dentition were compared to untreated sides, DH showed a difference in disease activity (> or =2 mm attachment loss) from 19.3% (untreated) to 7.2% (treated); and SRP from 14.3% (untreated) to 8.1% (treated). CONCLUSIONS: Results show that both DH without concomitant mechanical instrumentation and SRP were equally effective as SPT in this patient group over the 9-month study period.

Histologic evaluation of the periodontium of abutment teeth in combination implant/tooth fixed partial denture.

The histologic response of the periodontal tissues of teeth rigidly joined to implants with a fixed partial denture was evaluated using light microscopy. The fourth premolar of a dog was connected to implants placed in the first and second premolar position with a fixed partial denture. The restored teeth were under function for periods of 6, 12, 18, and 24 months, with unrestored fourth premolars as controls. The histology of the periodontal ligament on the fourth premolar was found to be similar in the control and the restored teeth. The periodontal tissues contained a minimal amount of inflammatory cell infiltrate. The crestal bone was cortical in nature, showing no periodontal breakdown. The orientation of the periodontal fibers was easily determined, indicating that minimal remodeling had taken place. The number and morphology of the blood vessels were also similar in the control and the treated teeth. The lack of inflammation and stability of the periodontal tissue suggested that the use of combination implant-to-natural-teeth restorations with rigid joints in this animal model does not result in deleterious effects on the periodontal tissues and that the forces placed on the tissues are within the remodeling capabilities of the teeth.

Electron microscopy of bone response to titanium cylindrical screw-type endosseous dental implants.

This study investigated the undecalcified bone and enveloping tissues supporting commercially pure titanium one-stage and two-stage endosseous dental implants placed into the mandibles of adult mongrel dogs. Correlative light microscopy, transmission electron microscopy, and high-voltage transmission electron microscopy demonstrated a dynamic bone interface to the implants. Mineralized tissue was routinely observed within 20 to 50 nm from the implant interface, separated from the implant interface only by an electron-dense deposit. The densely mineralized collagen fiber matrix was oriented parallel to the implant interface, as were osteocytes that were found close to the interface. Osteocytic projections progressed through canaliculi, often directly to the implant interface. Unmineralized areas that appeared to have the potential for mineralization were also identified.

Comparative implant research in dogs: prosthodontic protocol using two-stage ceramic endosseous dental implants.

This report describes one phase of a long-term comparative implant investigation involving 20 of 120 endosseous implants placed in 30 adult mongrel dogs. Fixed prostheses involving 16 of the 20 (4 control implants) two-stage ceramic endosseous implants have been provided using routine prosthodontic procedures and the limited prosthetic components available for the Bioceram Series II implant system. The prostheses have proven to be functional with minimal maintenance. To date, after 1 year of follow-up, 2 of the two-stage implants have exhibited problems caused by fracture of the hexagonal collar. None of the implants to date has been lost and none of the fixed prostheses has required re-cementation or any other type of maintenance other than normal hygiene. Clinical evaluation suggests continued implant and prosthesis serviceability after 1 year in function.

Composite morphology of the bone and associated support-tissue interfaces to osseointegrated dental implants: TEM and HVEM analyses.

Correlated transmission electron and high-voltage electron microscopic analyses examined the undecalcified bone and associated support tissues of 60 endosseous titanium blade and titanium and ceramic root-form implants in dogs. The implants supported fixed partial dentures for up to 2 years. Data obtained from this investigation suggest that a range of tissues, both mineralized and unmineralized, support osseointegrated dental implants. This study examined the tissues apposing not just isolated aspects of the implant surface, but the entire length of the implant, and found that mineralized and unmineralized tissues existed concurrently. Much of the implant surface was apposed by mandibular bone, and both root-form and blade implants osseointegrated. The densely mineralized collagen fibril matrix was often separated from the implant by only a 20-nm to 50-nm electron-dense, ruthenium-positive deposit. High-voltage electron microscope stereology demonstrated that cellular processes extended directly to the implant from underlying osteocytes. In the same implants, areas containing an unmineralized collagen matrix interposed between the bone and implant surface were observed. In this region osteoblasts interacted with this matrix, and Howship's lacunae, containing vascular elements and osteoclasts, were also observed. The remodeling activities appear to be a homeostasis of catabolic activity (osteoclasts) and metabolic activity (osteoblasts). The apex of the implant was often apposed by a fibrofatty stroma. The support tissue response appears to be the result of the interrelations of osteoblasts, osteocytes, and osteoclasts in association with vascular elements. Therefore, the support tissue response to osseointegrated implants is a dynamic activity that involves the healthy interaction of these cells and tissues along the entire length of the implant.