Progression Of Alveolar Bone Loss Research Articles

Effect of obesity on alveolar bone loss in experimental periodontitis in Wistar rats

Obesity has been linked to higher inflammatory status and periodontal breakdown.Objective The purpose of this study was to investigate the effect of obesity on alveolar bone loss in experimental periodontitis in rats. Material and Methods Twenty-four female Wistar rats were randomly divided into two groups: obese (n=13), which were fed with "cafeteria diet" (CAF diet - high amounts of sucrose and fat) for 90 days in order to gain weight, and non-obese (n=11) regularly fed rats. Ligature-induced experimental periodontitis was created in all animals. Body weight differed statistically between obese and non-obese groups (277.59 and 223.35 g, respectively) at the moment of the ligature placement. Morphometric registration of alveolar bone loss was carried out after 30 days of ligature placement to determine the effect of obesity on the progression of experimental periodontitis. Results Intra-group comparisons showed significantly higher alveolar bone loss mean values in maxillary teeth with ligature (P<0.05). Alveolar bone loss [mean (SD), mm] was not statistically different between obese and non-obese groups [0.71 (0.09) and 0.65 (0.07) mm, respectively]. However, when palatal sides are analyzed separately, obese group presented significantly higher alveolar bone loss (P<0.05) as compared to non-obese [0.68 (0.12) and 0.53 (0.13) mm, respectively]. Conclusions In spite of the weak differences, it is possible to conclude that the progression of alveolar bone loss in ligature-induced periodontitis can be potentially influenced by body weight in rats.

Using tetracyclines to treat osteoporotic/osteopenic bone loss: From the basic science laboratory to the clinic

Periodontitis (progressive inflammatory disease characterized by alveolar bone loss, a major cause of tooth loss worldwide) is associated with both systemic osteoporosis and its milder form, osteopenia. Tetracyclines, by virtue of their non-antimicrobial pro-anabolic and anti-catabolic properties, are excellent candidate pharmaceuticals to simultaneously treat these local and systemic disorders. This paper reviews the foundational basic science and translational research which lead to a pivotal multicenter randomized clinical trial in postmenopausal women with both periodontitis and systemic (skeletal) osteopenia. This trial was designed primarily to examine whether subantimicrobial dose doxycycline (SDD) could reduce progressive alveolar (oral) bone loss associated with periodontitis and, secondarily, whether SDD could reduce systemic bone loss in the same subjects. This paper describes the efficacy and safety findings from this clinical trial and also outlines future directions using this promising and novel approach to manage both oral and systemic bone loss.

Tooth Loss and Periodontal Disease Predict Poor Cognitive Function in Older Men

To determine whether rates of tooth loss, periodontal disease progression, and caries incidence predict cognitive decline in men. Prospective study. Community-dwelling men enrolled in the Veterans Affairs Dental Longitudinal Study. Five hundred ninety-seven dentate men aged 28 to 70 at study baseline who have been followed up to 32 years. Oral examinations were conducted approximately every 3 years. Periodontal disease measures included probing pocket depth and radiographic alveolar bone height. Participants underwent cognitive testing beginning in 1993. Low cognitive status was defined as less than 25 points or less than 90% of the age- and education-specific median on the Mini-Mental State Examination (MMSE) and less than 10 points on a spatial copying task. Each tooth lost per decade since the baseline dental examination increased the risks of low MMSE score (hazard ratio (HR)=1.09, 95% confidence interval (CI)=1.01-1.18) and low spatial copying score (HR=1.12, CI=1.05-1.18). Risks were greater per additional tooth with progression of alveolar bone loss (spatial copying: HR=1.03, CI=1.01-1.06), probing pocket depth (MMSE: HR=1.04, CI=1.01-1.09; spatial copying: HR=1.04, CI=1.01-1.06), and caries (spatial copying: HR=1.05, CI=1.01-1.08). Risks were consistently higher in men who were older than 45.5 at baseline than in younger men. Risk of cognitive decline in older men increases as more teeth are lost. Periodontal disease and caries, major reasons for tooth loss, are also related to cognitive decline.

Root Proximity as a Risk Factor for Progression of Alveolar Bone Loss: The Veterans Affairs Dental Longitudinal Study

The purpose of the present longitudinal study was to evaluate the association between root proximity and the risk for alveolar bone loss (ABL). We used data from the Veterans Affairs Dental Longitudinal Study, a closed-panel longitudinal cohort study of 1,231 men enrolled in 1968 with triennial follow-up examinations. Periapical radiographs of mandibular incisors from subjects with > or =10 years of follow-up were selected. Interradicular distance (IRD) at the cemento-enamel junction and alveolar bone levels at baseline and last follow-up were measured using digitized radiographs. The rate of progressive ABL was determined and expressed as millimeters per 10 years. Site-specific multivariate regression models were fit to evaluate the association between IRD and ABL rate, adjusting for age and smoking. Empirical standard errors and generalized estimating equations were used to account for the correlation among sites within subjects. There were 473 dentate subjects, aged 28 to 71 years at baseline, with > or =10 years of follow-up data available for analyses. The mean follow-up time was 23 years. The mean IRD was 1.0 +/- 0.3 mm, and the mean ABL rate during 10 years was 0.61 +/- 0.59 mm. There was a significant non-linear association between IRD and ABL rate (P <0.005). Compared to sites with IRD > or =0.8 mm, sites with IRD <0.6 mm were 28% (95% confidence interval [CI]: 11% to 48%) more likely to lose > or =0.5 mm of bone during 10 years (relative risk: 1.28 [95% CI: 1.11 to 1.48]) and 56% (95% CI: 11% to 117%) more likely to lose > or =1.0 mm of bone during 10 years (relative risk: 1.56 [95% CI: 1.11 to 2.17]). IRD <0.8 mm is a significant local risk factor for alveolar bone loss in mandibular anterior teeth. Measurement of IRD may have important prognostic value in making treatment decisions.

Effect of body weight in the pathogenesis of ligature-induced periodontal disease in Wistar rats

Objective. The aim of this study was to compare ligature-induced alveolar bone loss between obese and non-obese rats. Material and methods. Thirty female Wistar rats were randomly divided into two groups: a test group comprising 14 rats fed with a “cafeteria diet” for 120 days in order to gain weight and a control group comprising 16 regularly fed rats. Ligatures were placed around the 2nd upper molars, and the contralateral teeth served as intra-group controls. After 30 days, the animals were killed and the maxillae were removed. Sodium hypochlorite was used to prepare the specimens, and the cementum-enamel junction was stained with methylene blue 1%. Morphometric analysis of alveolar bone loss was by standardized digital photographs and the distance between the cementum-enamel junction and the alveolar bone crest was measured using the software Image Tool 3.0. Results. Body weight differed statistically between test and controls (268.6 and 242.4 g, respectively). Test animals demonstrated a mean (SD) alveolar bone loss of 0.51 (0.11) mm and in the controls 0.52 (0.14) mm in teeth with ligatures. No statistically significant differences were observed (ANOVA+Tukey), except for teeth with and without ligatures in both groups. Conclusions. The establishment and progression of alveolar bone loss in rats was not influenced by body weight in the present study.

RANKL Inhibition Through Osteoprotegerin Blocks Bone Loss in Experimental Periodontitis

Prevention of alveolar bone destruction is a clinical challenge in periodontal disease treatment. The receptor activator of nuclear factor-kappa B ligand (RANKL) inhibitor osteoprotegerin (OPG) inhibits osteoclastogenesis and suppresses bone resorption. To study the effects of RANKL inhibition on alveolar bone loss, an experimental ligature-induced model of periodontitis was used. A total of 32 rats were administered human OPG-Fc fusion protein (10 mg/kg) or vehicle by subcutaneous delivery twice weekly for 6 weeks. Negative or positive controls received no treatment or disease through vehicle delivery, respectively. Biopsies were harvested after 3 and 6 weeks, and mandibulae were evaluated by microcomputed tomography (microCT) and histology. Serum levels of human OPG-Fc and tartrate-resistant acid phosphatase-5b (TRAP-5b) were measured throughout the study by enzyme-linked immunosorbent assay (ELISA). Statistical analyses included analysis of variance (ANOVA) and Tukey tests. Human OPG-Fc was detected in the sera of OPG-Fc-treated animals by 3 days and throughout the study. Serum TRAP-5b was sharply decreased by OPG-Fc treatment soon after OPG-Fc delivery and remained low for the observation period. Significant preservation of alveolar bone volume was observed among OPG-Fc-treated animals compared to the controls at weeks 3 and 6 (P <0.05). Descriptive histology revealed that OPG-Fc significantly suppressed osteoclast surface area at the alveolar crest. Systemic delivery of OPG-Fc inhibits alveolar bone resorption in experimental periodontitis, suggesting that RANKL inhibition may represent an important therapeutic strategy for the prevention of progressive alveolar bone loss.

Immunization of Macaca fascicularis against experimental periodontitis using a vaccine containing cysteine proteases purified from Porphyromonas gingivalis

Periodontitis is a common infectious disease to which Porphyromonas gingivalis has been closely linked, in which the attachment tissues of the teeth and their alveolar bone housing are destroyed. We conducted a study to determine if immunization using a purified antigen could alter the onset and progression of the disease. Using the ligature-induced model of periodontitis in Macaca fascicularis, we immunized five animals with cysteine protease purified from P. gingivalis and used an additional five animals as controls. Alveolar bone loss was measured by digital subtraction radiography. Immunization induced high titers of specific immunoglobuin G serum antibodies that were opsonic. Total bacterial load, levels of P. gingivalis in subgingival plaque and levels of prostaglandin E(2) in gingival crevicular fluid were significantly reduced. Onset and progression of alveolar bone loss was inhibited by approximately 50%. No manifestations of toxicity were observed. Immunization using a purified protein antigen from P. gingivalis inhibits alveolar bone destruction in a ligature-induced periodontitis model in M. fascicularis.

Inflammation-induced Bone Remodeling in Periodontal Disease and the Influence of Post-menopausal Osteoporosis

During physiological conditions, the skeleton is remodeled in so-called bone multi-cellular units. Such units have been estimated to exist at 1-2 x 10(6) sites in the adult skeleton. The number and activities of these units are regulated by a variety of hormones and cytokines. In post-menopausal osteoporosis, lack of estrogen leads to increased numbers of bone multi-cellular units and to uncoupling of bone formation and bone resorption, resulting in too little bone laid down by osteoblasts compared with the amount of bone resorbed by osteoclasts. Inflammatory processes in the vicinity of the skeleton, e.g., marginal and apical periodontitis, will affect the remodeling of the nearby bone tissue in such a way that, in most patients, the amount of bone resorbed exceeds that being formed, resulting in net bone loss (inflammation-induced osteolysis). In some patients, however, inflammation-induced bone formation exceeds resorption, and a sclerotic lesion will develop. The cellular and molecular pathogenetic mechanisms in inflammation-induced osteolysis and sclerosis are discussed in the present review. The cytokines believed to be involved in inflammation-induced remodeling are very similar to those suggested to play crucial roles in post-menopausal osteoporosis. In patients with periodontal disease and concomitant post-menopausal osteoporosis, the possibility exists that the lack of estrogen influences the activities of bone cells and immune cells in such a way that the progression of alveolar bone loss will be enhanced. In the present paper, the evidence for and against this hypothesis is presented.

Quantitative gene expression profiling implicates genes for susceptibility and resistance to alveolar bone loss.

Periodontal disease is one of the most prevalent chronic inflammatory diseases. There is a genetic component to susceptibility and resistance to this disease. Using a mouse model, we investigated the progression of alveolar bone loss by gene expression profiling of susceptible and resistant mouse strains (BALB/cByJ and A/J, respectively). We employed a novel and sensitive quantitative real-time PCR method to compare basal RNA transcription of a 48-gene set in the gingiva and the spleen and the subsequent changes in gene expression due to Porphyromonas gingivalis oral infection. Basal expression of interleukin-1 beta (Il1b) and tumor necrosis factor alpha (Tnf) mRNA was higher in the gingiva of the susceptible BALB/cByJ mice than in the gingiva of resistant A/J mice. Gingival Il1b gene expression increased further and Stat6 gene expression was turned on after P. gingivalis infection in BALB/cByJ mice but not in A/J mice. The basal expression of interleukin-15 (Il15) in the gingiva and the basal expression of p-selectin (Selp) in the spleen were higher in the resistant A/J mice than in the susceptible BALB/cByJ mice. In the resistant A/J mice the expression of no genes detectably changed in the gingiva after infection. These results suggest a molecular phenotype in which discrete sets of differentially expressed genes are associated with genetically determined susceptibility (Il1b, Tnf, and Stat6) or resistance (Il15 and Selp) to alveolar bone loss, providing insight into the genetic etiology of this complex disease.

Effect of Selective Cyclooxygenase‐2 Inhibition on the Development of Ligature‐Induced Periodontitis in Rats

The purpose of this study was to evaluate the effect of a selective cyclooxygenase-2 inhibitor on the progression of alveolar bone loss in an experimental periodontitis model in rats. One hundred eighty (180) Wistar rats were separated into 3 experimental groups. Cotton ligatures were placed at the gingival margin level of lower right first molars. The rats were randomly assigned to one of the following groups that received: a daily oral dose of 10 mg/kg body weight of celecoxib (Ce1); 20 mg/kg body weight of celecoxib (Ce2); or 10 ml/kg of saline solution (C). Serum levels of celecoxib and white blood cell count were determined. Standardized digital radiographs were taken after sacrifice at 3, 5, 10, 18, and 30 days to measure the amount of bone loss around the mesial root surface of the first molar tooth in each rat. Two-way analysis of variance (ANOVA) indicated that groups treated with celecoxib had significantly less bone loss compared to controls (P < 0.0001) and that there was a significant interaction between treatment with celecoxib and time (P < 0.03). Post-hoc comparisons showed that in both groups treated with celecoxib, the bone loss became significant only after 10 days of ligature placement, while in the control group it was already significant after 5 days. However, differences in mean bone loss between control and Ce1 were significant only at 18 days and, between control and Ce2, at 5 and 18 days. There was no significant difference in bone loss among experimental groups at the end of the experimental period. These data provide evidence that systemic therapy with celecoxib can modify the progression of experimentally induced periodontitis in rats.

Three-dimensional evaluation of periodontalremodeling during orthodontic treatment

In 21 adult patients, two or three high-resolution computed tomography(HR-CT) examinations were performed before, during and after orthodontic treatment with fixed appliances. The time between the first, second, and third CT scanning varied according to the individual treatment or retention period from 12 to 36 months. Comparison of the CT examinations permits three-dimensional evaluation of osteoblastic and osteoblastic periodontal remodeling. The incidence of periodontal lesions, such as bone dehiscenses, fenestrations and root resorptions were assessed in relation to the initial periodontal situation and the applied orthodontic biomechanics. Anatomic risks were a small alveolar process, thin buccal or lingual bone plates, eccentric positioning of teeth, basally extended maxillary sinus, and progressive alveolar bone loss. Therapeutic risks were uncontrolled sagittal or vertical movements of the incisors and cortical or intermaxillary anchorage preparation. Orthodontically induced bone dehiscences were partly repaired by osteoblastic periodontal remodeling in the retention period.

The periodontal-systemic connection: implications for treatment of patients with osteoporosis and periodontal disease.

Osteoporosis and osteopenia may influence periodontal disease and tooth loss. Medications such as hormone replacement therapy and nutritional supplements that are used to prevent or treat osteoporosis have been evaluated for beneficial effects on oral health in a small number of human studies. Hormone replacement therapy (HRT), which slows the rate of bone loss at skeletal sites such as the hip and spine, also appears to reduce the rate of alveolar bone loss in postmenopausal women. HRT use is consistently associated with greater tooth retention and a reduced likelihood of edentulism in studies of elderly women. The number of studies on the effects of calcium or vitamin D intake on oral outcomes is limited, but suggest that higher intake levels are associated with reduced prevalence of clinical attachment loss and lower risk of tooth loss. Data from a prospective study of oral health in men show a similar association between higher calcium intake and reduced alveolar bone loss. The number of teeth with progression of alveolar bone loss over a 7-year period was significantly lower among men whose calcium intake was at least 1,000 mg per day, compared to men with a calcium intake below this level. Future studies should confirm these findings and evaluate the oral effects of new medications for osteoporosis. If confirmed, the implications for dental professionals may include an expanded array of medications for the treatment of periodontal disease and a greater emphasis on nutrition education for patients.

ALVEOLAR BONE LOSS AND TOOTH LOSS IN MALE CIGAR AND PIPE SMOKERS

While cigarette smoking is recognized as being detrimental to oral health, the effects of cigar and pipe smoking on tooth-loss risk, alveolar bone loss and periodontal disease are not known. The authors conducted this study to determine whether cigar and pipe smokers were at greater risk of experiencing tooth loss and alveolar bone loss than were nonsmokers. The authors studied 690 dentate men who participate in the Veterans Affairs Dental Longitudinal Study. Subjects are not VA patients, and they receive medical and dental care in the private sector. A board-certified periodontist conducted clinical examinations triennially for 23 years. These examinations included the number of teeth remaining, number of decayed and filled surfaces per tooth, and indicator scores for plaque, calculus, pocket probing depth, gingival bleeding and tooth mobility. Alveolar bone loss was assessed at each examination on intraoral periapical radiographs using the Schei ruler method, which measures loss of bone height in 20 percent increments. Multivariate analyses of tooth-loss rates and alveolar bone loss controlled for demographic and oral hygiene measures. The relative risk, or RR, of tooth loss compared with that of nonsmokers was significantly elevated in cigar smokers (RR = 1.3, 95 percent confidence interval, or CI, = 1.2, 1.5), pipe smokers (RR = 1.6, 95 percent CI = 1.4, 1.9) and cigarette smokers (RR = 1.6, 95 percent CI = 1.5, 1.7). The percentages of mesial and distal sites with moderate-to-severe progression of alveolar bone loss (a change of 40 percent or more from baseline) were 8 +/- 1 percent (mean +/- standard error) in nonsmokers, 16 +/- 3 percent in cigar smokers (P < .05), 13 +/- 4 percent in pipe smokers (P = .17), and 16 +/- 3 percent in cigarette smokers (P < .001). Pipe and cigar smokers did not differ significantly from nonsmokers with respect to the percentage of sites at baseline with moderate-to-severe scores for calculus, pocket probing depth, gingival bleeding or tooth mobility. Pipe smokers had fewer sites with moderate-to-severe plaque accumulation than did nonsmokers (7 +/- 11 vs. 13 +/- 17, P < .05). The authors found that men who smoke cigars or pipes were at increased risk of experiencing tooth loss. Cigar smokers also were at increased risk of experiencing alveolar bone loss. These elevations in risk are similar in magnitude to those observed in cigarette smokers. The increases in risk related to cigar and pipe smoking provide a strong rationale for targeting smoking prevention and smoking cessation programs to smokers of all tobacco products.

Potential application of low-dose doxycycline to treat periodontitis in post-menopausal women.

The purpose of this paper is two-fold: (1) to review the evidence that osteoporosis and post-menopausal estrogen deficiency are associated with progressive alveolar bone loss and an elevated risk of tooth loss; and (2) to propose the use of tetracyclines, specifically low-dose doxycycline (LDD) (and, perhaps in the future, the chemically modified tetracyclines), to mitigate alveolar bone loss in post-menopausal osteoporotic/osteopenic women. Design concepts for a randomized clinical trial to study the effects of LDD on progressive alveolar bone loss in this patient population are reviewed. Since osteoporosis affects over 20 million people in the United States, progressive alveolar bone loss in this patient group represents a potentially significant public health problem unique from common adult periodontitis. Stopping progressive alveolar bone loss is essential to prevent both tooth loss and micro-architectural deterioration of alveolar bone.

Circulating promyelocytes and low levels of CD16 expression on polymorphonuclear leukocytes accompany early-onset periodontitis.

Early-onset periodontitis (EOP) is characterized by rapidly progressive alveolar bone loss, chemotactic defects of neutrophils, and significant familial aggregation. We found immature myeloid lineage cells, defined as promyelocytes, in the peripheral blood in patients with EOP. A hematological examination of peripheral blood cells showed normal reference values regarding cell proportions. Flow cytometry revealed significantly lower expression of CD16, a glycosylphosphatidylinositol (GPI)-anchored protein, on peripheral neutrophils in patients compared with those in age- and sex-matched healthy controls, whereas the levels of CD11a and CD11b expression were similar. The chemotactic response of neutrophils was lower toward not only formyl-methionyl-leucyl-phenylalanine but also complement fragment C5a than that of healthy controls. The expression of another GPI-anchored protein, CD14, was equally expressed by controls and patients. Therefore, the low level of CD16 expression was not due to the incomplete synthesis of the GPI anchor. GPI anchors of CD16 on neutrophils from controls and patients were both partially resistant to phosphatidylinositol-specific phospholipase C. The presence of promyelocytes in peripheral blood, low expression of CD16, and low chemotactic response of neutrophils suggest that patients with EOP have an abnormal maturation system in myeloid lineage cells in the bone marrow, which may be associated with the onset and course of EOP.

The use of ketorolac tromethamine oral rinse for the treatment of periodontitis in adults

Periodontitis is a chronic infectious and inflammatory disease which afflicts approximately three quarters of the world’s adult population over the age of thirty-five. Recently published studies have demonstrated that long-term administration (>-6 months) of non-steroidal anti-inflammatory drugs (NSAIDs) can halt the progressive loss of alveolar bone associated with this disease. The safe and efficacious twice daily use for six months of 0.1% ketorolac tromethamine oral rinse for the prevention of periodontal disease progression in adults has recently been demonstrated. This presentation summarizes our results to date regarding the pharmacokinetics, pharmacodynamics, safety and efficacy of the topical oral rinse form of this potent NSAID in patients with periodontitis.

Unusual Gingival Enlargement With Rapidly Progressive Periodontitis. Report of a Case

A 15-year-old female patients suffered from recurrent unusual enlargement of the gingiva together with rapidly progressive alveolar bone loss. The enlarged gingiva completely covered her anterior teeth and protruded from the mouth. Marked inflammatory edematous tissue, which predominantly contained plasma cells, was observed in the connective tissue. Rapidly progressive alveolar bone loss was observed radiographically. The serum antibody titer to Porphyromonas gingivalis, measured by ELISA, was much higher than that in healthy individuals. The diagnosis was unusual gingival enlargement with rapidly progressive periodontitis. Conventional periodontal therapy, including plaque control, scaling, root planing, and surgical removal of the soft tissue, did not produce complete healing of the gingival lesion, although recurrence of gingival enlargement and further loss of the periodontal attachment level were well controlled. After the periodontal treatments, the serum antibody titer to P. gingivalis decreased to normal levels. This unusual gingival enlargement was considered due to systemic factors that exaggerated the gingival response to local irritation and altered the usual clinical features of chronic gingivitis; local plaque irritation produced the extensive and recurrent enlargement of the gingiva. Under these circumstances, infection or overgrowth of periodontopathic bacteria, including P. gingivalis, might occur and the alveolar bone loss would then advance very rapidly.

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.

Fluoride intake and alveolar bone loss in periodontal disease-susceptible mice.

The ability of a high F intake to inhibit alveolar bone loss was assessed over a period of one year in strain STR/N mice. This strain is susceptible to periodontal disease in the absence of dietary or traumatic stimuli, with progressive alveolar bone loss beginning in adulthood. Despite a very high bone F level, alveolar bone loss was not significantly different from that occurring in mice of the same strain with a low F intake. The resistance of alveolar bone to destruction does not appear to be a major factor in the progression of periodontal disease.

Effect of streptococcal cell wall components on bone metabolism in vitro

Cell was components from Streptococcus mutans NCTC 10449 and Streptococcus sanguis ATCC 10558 stimulated the release of 45Ca from prelabeled mouse calvariae in organ culture. Bone resorbing activity was not blocked by fetal calf serum. It was, however, blocked by calcitonin, an inhibitor of osteoclast-mediated bone resorption. Indomethacin, a prostaglandin synthetase inhibitor, partially blocked endogenous but not antigen-stimulated 45Ca, suggesting that antigen-stimulated bone resorption was not mediated by prostaglandins. The antigen preparations also had an inhibitory effect on the incorporation of 3H-proline and 3H-thymidine into explants of rabbit and rat calvariae, respectively. The inhibitory effect of antigen on 3H-proline incorporation was not altered by the presence of calcitonin, which suggests that it represented a real inhibition of protein synthesis and not a reflection that the bones were resorbing. These findings indicate that plaque bacterial antigens may contribute directly to the progressive loss of alveolar bone during periodontal disease. The assumption that only Gram-negative organisms play an important role In the etiology of periodontal disease appears incorrect.