Flurbiprofen: a potent inhibitor of alveolar bone resorption in beagles.

The nonsteroidal anti-inflammatory drug, flurbiprofen, a potent cyclooxygenase inhibitor, significantly decreases the resorption of alveolar bone in naturally occurring chronic destructive periodontal disease in beagles. This observation indicates that arachidonic acid metabolites are important in the alveolar bone loss of periodontitis and suggests a use for flurbiprofen in the management of bone resorption disease.

Bone loss in the oral cavity.

Bone loss in the oral cavity may occur due to many causes, including infection, systemic or local alterations in the host response, or multifactorial causes. The purpose of this article is to review our present understanding of the major causes of oral bone loss in adults, with special emphasis on two major oral diseases: periodontitis and residual ridge resorption. Periodontitis is characterized by resorption of the alveolar bone as well as loss of the soft tissue attachment to the tooth. Progressive periodontitis will result in continued alveolar bone loss and may result in tooth mobility, abscesses, and ultimately tooth loss. Although the reported prevalence may vary according to the epidemiologic study design, the 1985 National Survey of Oral Health of United States Adults indicated that 94% of female senior citizens examined demonstrated at least one site with at least 2 mm loss of attachment. Resorption of alveolar bone that occurs following tooth extraction is termed residual ridge resorption. In many cases, the denture will loosen because of the inability of the resorbed ridge to stabilize the prosthesis. In the most severe cases, the denture may impinge on the exposed mandibular nerve, resulting in pain or total inability to tolerate the prostheses. Although clear statistics on the prevalence of residual ridge resorption are not available, this boss loss may result in the need for new dentures to replace ill-fitting prostheses.

Indium and iron as tracers for erythroid precursors.

External visualization and delineation of functional bone marrow is important for diagnostic, prognostic and therapeutic purposes. Because of difficulties in using the isotopes of iron for bone-marrow imaging, indium-111 chloride has been used extensively for this purpose. In this investigation we attempted to solve the problem of cellular localization of indium chloride by employing a rat model with erythropoietic precursors selectively damaged by lethal intracellular radiation from the Auger electrons of Fe-55. In the rat, we have shown that the absolute marrow uptakes of indium and iron are different, whereas the absolute uptakes of indium and sulfur colloid are the same. However, in animals whose erythroid activity was partially destroyed with Fe-55, the fractional depressions of iron and indium uptakes were the same and corresponded to the extent of the remaining erythroid activity. In addition, following an in vitro separation of the cellular elements of marrow with iron carbonyl, both iron and indium were found in the erythroid-rich supernatant, whereas sulfur colloid was in the precipitate. These results indicate that, in the rat, In-111 chloride is an effective in vivo marker for the early phases of iron uptake by the bone marrow.

Effects of nonsteroidal antiinflammatory drugs on bone loss in chronic inflammatory disease.

Several controlled clinical trials have indicated that nonsteroidal antiinflammatory drugs may slow alveolar bone loss in periodontitis. Demonstration of this efficacy is dependent on the development of accurate, sensitive, and specific quantitative methods for the assessment of bony change, such as digital subtraction radiography. Further studies of such methodologies are required to more fully investigate the effect of nonsteroidal antiinflammatory drugs in rheumatoid arthritis.

Semiconductor probe measurements in beagle dogs with periodontal disease.

A miniaturized semiconductor probe was used to measure alveolar bone uptake of a bone-seeking radiopharmaceutical in dogs with destructive periodontal disease. Radiopharmaceutical uptake in localized, advanced disease was greater than in incipient disease and was generalized, with increased uptake occurring in radiographically normal areas and in areas with bone loss.

Predicting alveolar bone loss in beagles using bone-seeking radiopharmaceutical uptake.

Measurements of bone-seeking radiopharmaceutical uptake obtained at the beginning of this two-year study of beagles with periodontal disease were correlated with the amount of bone loss which occurred during the study. Uptake correlated with bone loss (r = 85), which suggests that uptake may be an indicator of future bone loss.

Semiconductor probe measurements in beagle pups during deciduous tooth development.

Bone-seeking radiopharmaceuticals were used together with clinical and radiographic procedures to study tooth development in dogs. Similarities in the pattern and time course of radiopharmaceutical uptake in jaw areas studied suggest that changes in alveolar bone metabolism are not closely related to eruption times of individual teeth.

Detection of periodontal disease activity with a scintillation camera.

The goal of this study was to assess the ability of a scintillation camera method to detect areas of active bone loss due to periodontitis. Technetium 99m methylene diphosphonate was used as the bone-seeking radiopharmaceutical. Bone-seeking radiopharmaceutical uptake (BSRU) was imaged and quantified in alveolar bone regions of interest with a scintillation camera and a computer. Analysis of the sequential radiographs over six months constituted the basis for determination of sites of active disease. The study was composed of two parts. First, 18 subjects, nine with adult periodontitis and nine controls, were enrolled in a cross-sectional study to determine whether the quantitative scintillation amera methodology detected differences in BSRU in periodontitis vs. periodontally healthy patients. Second, the nine patients with periodontitis were studied longitudinally in order to determine whether the BSRU examination was indicative of bone loss subsequently measured radiographically. In the cross-sectional study, the mean uptake ratio for the periodontitis group was significantly higher than that for the control group (1.63 +/- 0.06 and 1.42 +/- 0.04, respectively, p less than 0.01, t test). From the longitudinal study, the mean patient scintillation image uptake ratios were highly correlated with the mean bone loss determined from serial radiographs (p less than 0.01). The accuracy, sensitivity, and specificity of the quantitative gamma camera method for detecting site(s) of active bone loss within the region of interest were assessed relative to the longitudinal radiographic data. The accuracy, sensitivity, and specificity were 85%, 90%, and 79%, respectively. Alveolar bone scintigraphy with a gamma camera and computer may provide a simple and valid technique for the immediate indication of areas of periodontal disease activity.

An adaptable head retention and alignment device for computed tomography scanning of Macaca mulatta.

An adaptable retention device has been developed for the purpose of holding and aligning the head of a sedated primate subject during computed tomography (CT) scan procedures. The device is used to obtain a close reproduction of CT scan studies at a time before and after dental implant placement in the mandibles of nine subjects. Geometric and material properties are extracted from these studies for the purpose of developing finite elements computer models. The device is constructed of low-density acrylic and consists of a horizontal base to which lateral supports are affixed. The device is placed on the CT table and axially aligned with the scan beam. Repeatable, calibrated CT studies of primate implant subjects were possible using the head holding device.

A periodontal probe with automated cemento--enamel junction detection-design and clinical trials.

An automated periodontal probe has been developed to measure pocket depth and attachment loss in a single measurement under controlled force conditions. A natural anatomic landmark, the cemento-enamel junction (CEJ), is used as a reference for attachment level measurements. The CEJ is detected automatically by immediate digital postprocessing of simultaneous measurements of probe tip acceleration and displacement during probing. Clinical trials in the beagle dog model for naturally occurring periodontitis have shown that the automated probe, when used with 35 g probing force, has a repeatability of 0.16 mm and a bias of 0.09 mm. These results indicate that the automated periodontal probe is capable of attachment level measurements with a high degree of repeatability and validity.

Principles and pitfalls of clinical trials design.

Periodontitis and gingivitis trials can involve many complex experimental designs. The selection of a specific design and the details of the protocol can influence the magnitude of any effect observed, the generalizability of the results, and the clinical significance of the findings. The purpose of this paper is to review selected aspects of clinical trials including the overall clinical experimental design, controls, outcomes, sample size, and patient selection. Particular emphasis will be placed on periodontitis trials.

Radiographic methods for the detection of progressive alveolar bone loss.

Intraoral transmission radiographs have been the primary diagnostic method for the assessment of bone support as well as for the detection and measurement of osseous changes due to periodontitis. The purpose of the present paper is three-fold. The first is to review radiographic techniques for the assessment of periodontal disease progression, presenting the strengths and weaknesses of each method while placing special emphasis on digital subtraction radiography. The second purpose is to present data from a recent study that compared the ability of digital subtraction radiography and automated attachment level probing to detect the same active sites. Thirty periodontitis patients and eight control patients were studied over a 6-month period. The results indicate that when these two sensitive methods for the assessment of progressive periodontitis were used there was concordance between the presence or absence of probing attachment loss and bone loss in 82.1% of the sites. The final goal of this paper is to present future directions for the quantitative analysis of digital radiographic images.

Alveolar bone destruction due to overhanging amalgam in periodontal disease.

Interproximal bone loss around 100 teeth with overhanging amalgam restorations was measured and compared to interpoximal bone loss around 100 contralateral teeth without overhanging amalgams. The latter served as controls. Overall, bone loss was found greater around teeth with overhangs (P < 0.01). This finding was true for all periodontal disease types. However, the more severe the periodontal disease the greater the role of the overhang appeared. Small overhangs, unlike medium and large overhangs, did not result in increased alveolar bone loss around the affected tooth.

Progression of probing attachment loss in adult periodontitis.

Thirty patients with adult periodontitis were monitored using an automated periodontal probe for 6 months in order to determine the prevalence of active sites and the overall pattern of disease progression in active sites. The automated probe is capable of measuring probing attachment levels relative to the cemento-enamel junction with better than 0.2 mm of accuracy. The prevalence of disease activity was dependent on the threshold for probing attachment loss used. When the smallest threshold (0.4 mm) was used the prevalence of active disease was 29%, whereas a large threshold (2.4 mm) detected only 2% active sites. Regression analysis of the active sites revealed that 76% of the sites lost probing attachment consistent with a continuous model for disease progression. A small subset of sites demonstrated either bursts of activity or exacerbations and remissions of disease activity.

Comparison between 2 surgical techniques for the treatment of early-onset periodontitis.

The objective of this study was to compare guided tissue regeneration (GTR) and osseous surgery (OS) in treatment of early-onset periodontitis. Six patients participated in this research, presenting 15 paired defects randomly assigned to 1 of the surgical groups. Pre-operative clinical parameters (probing depth and attachment loss) between the two groups were not significantly different. Results 1 year following surgery showed probing depth reduction (2.60 +/- 1.30 mm) and clinical attachment gain (2.20 +/- 1.42 mm) were significantly greater in the GTR group than in the osseous surgery group (P < 0.05). The gingival recession was -0.53 +/- 0.52 mm and -0.40 +/- 0.74 mm for the osseous and the guided tissue regeneration group, respectively (no significant difference, P > 0.05). Radiographic analysis by two techniques illustrated that the interproximal alveolar bone changes at the margin of the defects in the OS group were slightly decreased (-0.20 +/- 1.15; 0.26 +/- 0.74 mm) and those in the GTR group were slightly increased (0.16 +/- 0.96; 0.26 +/- 0.68 mm), but showed no significant difference (P > 0.05). The base of the GTR-treated defects showed significant increase in bone fill (1.67 +/- 0.68; 1.97 +/- 0.74 mm; P < 0.05). At a follow-up reexamination 1 year following surgery, oral hygiene and gingival conditions in both groups were at satisfactory levels and gingiva was clinically healthy throughout the entire study period, except the first 4 to 6 weeks following surgery.

Blur reduction of conventional film-based tomograms for pre-surgical evaluation of potential mandibular implant sites.

The usefulness of motion-based cross-sectional tomography to evaluate osseous support and adjacent anatomical structures for dental implant placement is limited by the inherent blurring in these images. The goal of this study was to develop a method to remove blurring while permitting accurate dimensional analysis of the potential implant site. Defined regions (anterior, cuspid, premolar, molar) on two preserved human mandibles were imaged using cross-sectional linear tomography. Algorithms were developed as a personal computer application to remove the blur and to aid in identification of the cortical plate borders and the mandibular canal. The data set of eight tomograms was digitized and the blur reduced with the developed algorithm. An operator measured the height and width of the mandible on each original tomogram and each deblurred tomogram in triplicate. Method error was calculated as the difference between direct caliper measurements of the respective skull regions and image measurements of height and width for both the original digitized tomograms and the deblurred tomograms. Method error using the original images (height: -2.72 +/- 2.15 mm; width: -0.58 +/- 1.36 mm) compared to the deblurred tomograms (height: -0.58 +/- 1.16 mm; width: 0.37 +/- 0.59 mm) was significantly greater for both height (t-test level of significance, P = 0.0047) and width (t-test level of significance, P = 0.0001). These findings suggest that the method developed may greatly improve the ability of clinicians to accurately assess the implant site using cross-sectional film-based linear tomograms.

Alveolar bone loss due to open interproximal contacts in periodontal disease.

Ninety patient records were examined in order to determine radiographically whether an association between open interproximal contacts and increased alveolar bone loss exists. The amount of alveolar bone in the open contact site was compared to the amount of alveolar bone in the contralateral closed contact site. Open interproximal contacts were not found to be associated with increased alveolar bone destruction in Class, I, III and IV periodontal disease groups. In group of 53 Class II cases, open contacts were found to be associated with an average of 2.4% less relative bone height than contralateral closed contacts. This difference was significant at the 0.01 to 0.02 level.

Nuclear medicine. An indicator of "active" alveolar bone loss in beagle dogs treated with nonsteroidal anti-inflammatory drug.

Nuclear medicine was used to assess the activity of alveolar bone loss in beagle dogs treated with the nonsteroidal anti-inflammatory drug flurbiprofen. Radiographic measurements of the rate of bone loss were taken during a 6-month "pretreatment" period and a 9-month treatment period. During the treatment period six dogs received a placebo, and six dogs received orally 0.02 mg/kg flurbiprofen daily for 9 months. In addition, each dog received periodontal surgery in one half of the mouth at the end of the pretreatment period. The rate of alveolar bone loss was significantly decreased in the treatment period in the flurbiprofen-treated dogs (P less than 0.001). Measurements of bone-seeking radiopharmaceutical uptake were taken 3 months after the initiation of therapy. The single measurement of uptake was compared to the rate of bone loss determined from repeated radiographs taken during the 9-month treatment period. Bone-seeking radiopharmaceutical uptake was an accurate indicator of "active" bone loss in 83.5% of the teeth studied.

Healing of spontaneous periodontal defects in dogs treated with xenogeneic demineralized bone.

This study was undertaken to histologically, clinically and radiographically evaluate the sequence of healing following implantation of bovine demineralized bone powder (DBP) into severe, spontaneous periodontal defects in beagle dogs. Eight dogs with documented severe periodontitis were treated surgically following initial debridement. One quadrant in each arch was treated with conventional flap surgery and the others were treated with surgery followed by DBP implantation. Animals received postoperative debridement and clinical and radiographic evaluation. Two dogs were sacrificed at 1, 3, 6 or 12 months postoperatively, and the jaws were evaluated histologically. Clinically, DBP was well tolerated by recipients. No evidence of localized inflammatory response or delayed hypersensitivity reaction was noted. Significant reductions in gingival inflammation were noted in both experimental and control sites at 1 month postoperatively compared to preoperative scores. Equivalent periodontal pocket reduction was noted between test and experimental sites and remained significant at 12 months. Radiographically, no differences were noted in the rate of bone loss between control and test sites. Histologic evaluation demonstrated the presence of DBP at 1 month following implantation, but the material was replaced with new bone by the next sacrifice period. Periodontal ligament fibers of standard orientation were seen extending from DBP-induced bone to the root surface by 1 month after implantation. An intact epithelial attachment appeared to be present 1 month after the implantation of DBP. No differences in root surfaces were detected between test and control groups. Ankylosis was a rare finding, noted equally between test and control sites. DBP did not appear to predispose to external root resorption. In later stages, histologic evidence of advancing periodontitis was noted equally in both control and experimental groups. While DBP successfully induced new bone formation, the inability to adequately maintain the periodontal tissues due to bacterial accumulation in this model combined with recurrent pocket formation, precluded any conclusion regarding long-term advantage. Based on these findings, clinical trials of this or similar materials are recommended.

Periodontal disease progression.

BACKGROUND: The objective of this investigation is to use noninvasive, state-of-the-art, diagnostic techniques to measure periodontal disease progression and model periodontal disease activity over time. In this investigation, digital subtraction radiography and an electronic controlled force periodontal probe capable of attachment level measurement were used to measure bone loss and attachment loss, respectively. The use of these nearly continuous measures of attachment and bone loss allowed detection of small amounts of disease activity and provided data to be used in modeling of the disease process over time. METHODS: Forty-four patients were studied for 18 months. Examinations used clinical attachment level measures at 1-month intervals and quantitative radiology at 6-month intervals. The sites were analyzed by regression for statistically significant changes. These data were used to determine sites of periodontal disease activity for testing various models of periodontal disease progression. RESULTS: Overall 22.8% of sites lost attachment, 5.4% gained, and 71.7% demonstrated no statistically significant change. The mean time to lose 1 mm of attachment was 8.4 +/- 0.6 months. In the first model tested a step-wise discriminant analysis was used to determine whether or not baseline measurements of plaque (PI), gingival inflammation (GI), attachment loss, and probing depth (PD) could be used to derive a satisfactory model for disease progression. Although the overall model was statistically significant with PI, PD, and GI contributing to the model (Wilks' lambda = 0.859, F = 5.71, P <0.0012), its predictive power was relatively weak. A considerably stronger significant model resulted when the rate of attachment loss over the first 6 months, baseline PI, and baseline GI were included (Wilks' lambda = 0.712, F = 14.17, P<0.00001). A significant model also resulted when bone loss during the first 6 months and baseline probing depth were included (Wilks' lambda = 0.438, F = 61.48, P<0.00001). When the last model was applied to each site, the sensitivity in predicting disease progression was 80.0% and the specificity in ruling out progressive disease was 93.9%. CONCLUSIONS: This study indicates that clinically significant progression of attachment loss in posterior tooth sites occurs as a frequent event in adult periodontitis. The modeling data also suggest that short-term (6 month) measures of periodontal disease progression greatly improve the ability to model attachment loss over a longer period in untreated periodontitis patients.