Neutrophil response to dental plaque by gender and race.

The inflammatory response, which has both genetic and environmental components, is a central mechanism linking oral and systemic diseases. We hypothesized that dental plaque accumulation over 21 days in the experimental gingivitis model would elicit systemic inflammatory responses [change in white blood cell (WBC) count and neutrophil activity], and that these responses would differ by gender/race. We recruited 156 healthy young adults, including black and white males and females. Plaque Index (PI), Gingival Index (GI), systemic WBC counts, and peripheral neutrophil oxidative activity were recorded. Overall, 128 participants completed the study. During the experimental phase, the correlation between PI and GI was 0.79. Total WBC and neutrophil counts did not change. Neutrophil activity increased in blacks but not whites, suggesting that there may be racial differences in the inflammatory response to dental plaque accumulation.

Hydroxyapatite/PMMA composites as bone cements.

Currently PMMA is the polymer most commonly used as a bone cement for the fixation of total hip prostheses. Ideally, a bone cement material should be easy to handle, biologically compatible, nonsupporting of oral microbial growth, available in the particulate and molded forms, easy to obtain, nonallergenic, adaptable to a broad range of dental and medical applications, in possession of high compressive strength, and effective in guided tissue regenerative procedures. One of the problems associated with the conventional types of bone cement used is their unsatisfactory mechanical and exothermic reaction properties. The purpose of this in vitro study was to investigate and compare the mechanical properties (three-point bending strength, energy-to-break, and modulus of elasticity) and physical properties (setting time, water sorption, and exothermic heat) of HA/PMMA (HA group) and bovine-bone originated HA/PMMA (BB group) composites. Composites samples were fabricated by admixing method. It was found that the addition of HA and BB particles increased the water sorption. Generally 10 v/o 20 v/o HA and 0 v/o to 10 v/o BB ratio combinations had significant beneficial effects on the mechanical properties. The heat generated during polymerization was influenced by the different admixtures. More than 40 v/o HA and 40 v/o BB should be mixed into PMMA to reduce the peak temperature. Overall evaluation indicated that the BB group had better properties than the HA group.

Oral Helicobacter pylori: can we stomach it?

Helicobacter pylori infection is one of the most common in man. The bacterium primarily resides in the human stomach, where it plays a significant role in gastric disease. If the spread of H. pylori is to be prevented, an understanding of the transmission process is essential. The oral cavity has been proposed as a reservoir for gastric H. pylori, which has been detected by culture and PCR in both dental plaque and saliva. This review will discuss the evidence for the role of the oral cavity in the transmission of gastric H. pylori. Moreover, the difficulties encountered in addressing this topic, possible directions for future research, and the implications for the dental profession are discussed.

Comparison of periodontal disease status of adults in two untreated indigenous populations of Guatemala, Central America.

OBJECTIVE: To compare the periodontal disease levels of two distinct indigenous populations of Guatemala, Central America, to determine whether differences exist. MATERIAL AND METHODS: Cross-sectional studies were performed in adults from the communities of San Juan La Laguna, SJLL (n = 125) and Tzununa (n = 54). In both cases, full-mouth pocket probing depths (PPDs) and clinical attachment levels (CALs) were measured by a single examiner, and the same examiner was employed in both studies. Recession at each site was derived from PPD and CAL measures. RESULTS: Tooth number did not differ significantly between SJLL and Tzununa (28.0 and 27.2, respectively). With respect to periodontal disease status, the percentage of sites with PPD >or= 5, 6 and 7 mm did not differ significantly, although mean PPD was significantly greater in the Tzununa sample (P = 0.01). Mean CAL and percentage of sites with CAL >or= 4, 5, 6 and 7 mm was significantly greater in SJLL than in Tzununa (P < 0.005) and the difference increased with age. Mean recession was also significantly greater in SJLL than Tzununa (P < 0.005), as was the percentage of sites with recession >or= 3 mm (P = 0.02), 4 mm (P = 0.002) and 5 mm (P = 0.008). CONCLUSION: The disease levels differed between these two indigenous Guatemalan communities. Whether this has a primarily environmental or genetic basis remains to be elucidated. :

Extending scientific horizons in the developing world - the Central American experience.

The juxtaposition of 'oral disease' and 'developing countries' invariably evokes thoughts of how one might assist these nations in attaining 'a healthy mouth for all' according to Western standards. In this discussion, the emphasis is shifted to consider collaborations between the industrial nations and those less developed countries, in the conduct and development of research. This potentially fruitful partnership can produce scientific, educational and cultural rewards for mutual benefit.

Subgingival microbiota of indigenous Indians of Central America.

OBJECTIVE: To define the subgingival microbial profiles of adult subjects from a previously identified rural community of indigenous Indians in Guatemala, Central America. MATERIALS AND METHODS: A full-mouth periodontal examination was performed in 114 adult subjects from 45 families. Plaque samples were collected from both deep and shallow periodontal pockets and checkerboard DNA-DNA hybridization was employed to identify 17 species previously associated with periodontitis or health. RESULTS: Plaque deposits and gingivitis were universal and widespread, and periodontal pocketing > or =5 mm was highly prevalent (84% of subjects). Streptococcus sanguis, Actinomyces naeslundii genospecies 2 and Fusobacterium nucleatum were significantly more prevalent in shallow sites. At the subject level, Actinomyces naeslundii and Peptostreptococcus micros were significantly more prevalent in periodontally-healthy subjects. Actinobacillus actinomycetemcomitans was not detected in any sample. CONCLUSION: There was no association between periodontal disease status and presence of suspected periodontal pathogens. These latter results conflict somewhat with those from treated populations. However, in this population where extensive plaque deposits and gingivitis are universal, the presence of putative pathogens may be more reflective of the local environment.

Oral health status of an indigenous adult population of Central America.

OBJECTIVE: To determine the caries experience and periodontal disease status in adults of an indigenous rural community of Guatemala, and assess the suitability for longitudinal investigations. BASIC RESEARCH DESIGN: This investigation comprised an initial screen (Study I) and a more detailed periodontal examination (Study II). In Study I, caries and gingivitis levels were determined. In Study II, pocket probing depths (PPDs) and clinical attachment levels (CALs) were recorded on all teeth excluding third molars. CLINICAL SETTING: Tzununa, Guatemala, Central America. PARTICIPANTS: Studies I and II were conducted in 120 adults 3 18 years and 54 adults 3 25 years respectively. RESULTS: In both Studies I and II, tooth retention was high with a mean tooth count of 28.2 and 27.2 respectively. Extensive soft deposits and both supra- and subgingival calculus were almost universal, although gingivitis was less than expected (Study I: Mean percentage of sites bleeding on probing = 27.6). In Study I, the mean number of carious teeth was 8.6 and there was no statistically significant correlation with age. In Study II, PPD 3 5mm and CAL 3 6mm were highly prevalent (100% and 56% of subjects respectively), although widespread and severe disease was not evident. CONCLUSIONS: Despite the high caries level and the evidence of periodontal destruction in the majority of subjects, all study subjects had a functional dentition suggesting that emergency treatment remains the current priority. Longitudinal studies in such untreated populations would provide increased understanding of the role of environmental factors in disease etiology. The study also highlighted some methodological issues pertinent to conducting studies in remote communities.

Periodontal disease status of an indigenous population of Guatemala, Central America.

OBJECTIVES: This study was designed to determine the periodontal disease status of an indigenous Indian community of rural Central America (San Juan La Laguna, Guatemala), for comparison with results of similar studies in other populations, and with a view to performing future studies to address familial clustering of adult periodontitis. METHODS & RESULTS: An initial screen of 239 subjects aged 12-75 years from extended families suggested a high disease prevalence according to full-mouth pocket probing depths (PPDs), with more than 75% of subjects with one or more pockets of PPD > or =5 mm. A more detailed study was performed in 125 unrelated subjects > or =18 years, recording full-mouth PPDs and clinical attachment levels (CALs). The high prevalence of pocketing was confirmed and 90% of adults > or =35 years had at least one site with CAL > or =6 mm. However, extensive disease was restricted to a small minority, with only 10% of adults > or =35 years having 20% or more sites with CAL > or =6 mm. CONCLUSION: The study results highlight the importance of performing a detailed examination and appropriate analysis. In both studies, tooth retention was high (mean number of teeth recorded was 26.4 and 28.0 respectively), smoking unusual, and families large and localised to the village. This community thus affords several advantages over populations in developed countries when considering familial studies of adult periodontitis.

Systemic neutrophil response resulting from dental plaque accumulation.

BACKGROUND: There is considerable current interest in putative relationships between oral and systemic diseases. Since the host response to oral bacteria may be the critical link in this association, our hypothesis was that dental plaque accumulation in healthy subjects would elicit a systemic inflammatory response. METHODS: Twenty-three healthy subjects, aged 18 to 25, participated in a 4-phase study. An initial hygiene phase was followed by a 21-day experimental phase (the so-called experimental gingivitis model) in which subjects refrained from all oral hygiene practices, thus permitting the accumulation of bacterial plaque. At days 0, 7, and 21 total and differential peripheral white blood cell (wbc) counts, together with full mouth plaque and gingivitis scores, were recorded. Following a 28-day recovery phase, in which normal oral hygiene practices were resumed, subjects entered the final 21-day control phase which mirrored the experimental phase but with subjects maintaining normal oral hygiene practices. RESULTS: The experimental model performed as anticipated with a correlation between plaque and gingivitis scores of 0.95, also reflecting subject compliance. Total wbc and neutrophil counts increased during the experimental phase. Furthermore, comparison of neutrophil counts between the experimental and control phases demonstrated a significantly higher cell count for the experimental phase on both days 7 and 21 (P= 0.0301 and 0.009, respectively). For total wbc, this was significant on day 21 (P= 0.0262). CONCLUSION: The results of this study support the hypothesis that the accumulation of dental plaque can result in a measurable systemic inflammatory response, providing further in vivo data to support a mechanistic relationship between oral and systemic pathology.

Effect of cellulose acetate materials on the oxidative burst of human neutrophils.

Following adverse clinical events involving seven patients undergoing renal dialysis using 12-year-old cellulose acetate hemodialyzers, this in vitro study was proposed in an effort to characterize the inflammatory response to the constituent cellulose acetate (CA) fiber materials. Chemiluminescence (CL) and apoptosis assays were used to determine whether human neutrophils were activated by CA fiber materials and/or are sensitive to degradation/alteration of these fibers over time. Furthermore, the study examined in vitro assays with human neutrophils using a CA film, the solvents used in the film preparation and CA resin. The film could be cut to identical sized pieces in an effort to compare hemodialysis material effects in standardized amounts. For the CL assays, 60-min exposure was followed by secondary stimulation with n-formyl-met-leu-phe (fMLP) or phorbol-12-myristate-13-acetate (PMA). Short-term exposure (60-min postintroduction to CA materials) increased the inflammatory response as measured by the respiratory burst of neutrophils (p < or =.05), with CA fiber exposure significantly compared with cells alone. There was a trend toward an increased response with exposure to older fibers with secondary PMA stimulation. Apoptosis was increased 12% with exposure to the more aged fibers versus 2% with the new fibers. The fiber storage component, glycerol, significantly inhibited the oxidative response (p < or =.001; > or =80% suppression with concentrations of 5-20%). The solvents used in film preparation, N,N-dimethylacetamide and tetrahydrofuran, produced greater than a 70% and 60% suppression, respectively, of CL activity for all concentrations > or =1%. More work is needed to determine the specific nature of the interaction of inflammatory cells with CA materials, but early evidence suggests that neutrophils are activated by CA and display an altered response to more aged fibers.

Helicobacter pylori infection in indigenous families of Central America: serostatus and oral and fingernail carriage.

Helicobacter pylori infection remains one of the most common in humans, but the route of transmission of the bacterium is still uncertain. This study was designed to elucidate possible sources of infection in an isolated, rural population in Guatemala. A total of 242 subjects in family units participated in the study. A medical history, including a history of dyspepsia, was taken by a physician and immunoglobulin G antibodies to H. pylori were detected with the QuickVue (Quidel, San Diego, Calif.) onsite serology test. Overall, 58% of subjects were seropositive, with a positive relationship between mother and child (P = 0.02) and a positive correlation between the serostatuses of siblings (intraclass correlation coefficient = 0.63). There was no association between serostatus and gastric symptoms. Oral H. pylori was detected from periodontal pockets of various depths and the dorsum of the tongue by nested PCR. Eighty-seven percent of subjects had at least one oral site positive for H. pylori, with the majority of subjects having multiple positive sites. There was no association between periodontal pocket depth and the detection of H. pylori. Nested PCR was also used to detect H. pylori from beneath the nail of the index finger of each subject's dominant hand. Overall, 58% of subjects had a positive fingernail result, with a significant positive relationship between fingernail and tongue positivity (P = 0.002). In conclusion, the results of this study suggest that oral carriage of H. pylori may play a role in the transmission of infection and that the hand may be instrumental in transmission.

Differential activation of human neutrophils by Streptococcus mutans isolates from root surface lesions and caries-free and caries-active subjects.

Phagocytosis of bacterial pathogens is an important defense mechanism and may contribute to regulating Streptococcus mutans-induced dental caries, particularly at root surfaces. This study was undertaken to examine and compare differences in polymorphonuclear leukocyte or neutrophil activation by clinical isolates of S. mutans collected from the saliva of caries-free or caries-active individuals with S. mutans isolates from root surface lesions. S. mutans clinical isolates (5 caries-free, 5 caries-active, 5 root caries isolates and a laboratory strain) were incubated with neutrophils in the presence of normal human serum and the luminol dependent chemiluminescence was measured for 1 h at 37 degrees C. Results indicated that the caries active and laboratory strains activated neutrophils equally. The mean integration stimulated by caries-free strains, however, displayed a 25-30% enhanced neutrophil activation over the caries-active and laboratory strains. In contrast, neutrophil activation by root caries strains of S. mutans was 45-50% lower than all other S. mutans strains, possibly suggesting a natural selection for S. mutans strains that can evade neutrophil recognition and subsequent phagocytosis. Stimulation of neutrophils with the cell wall and membrane surface component preparations indicated that extracts from all four groups activated neutrophils significantly. Again, caries-free preparations activated neutrophils significantly more than caries active, laboratory strain and root caries isolates. This selection may become more important on root surfaces due to increased exposure to crevicular fluid and neutrophils. The data provide evidence for the presence or onset of mechanisms or biological alterations in S. mutans developed to circumvent neutrophil recognition and/or phagocytosis, thus increasing S. mutans survival and colonization on tooth surfaces, resulting in an enhanced risk of dental caries, particularly at root surfaces.

Dose-dependent suppression of the neutrophil respiratory burst by lidocaine.

BACKGROUND: Oxygen radical production is thought to be fundamental to the pathogenesis of post-ischaemic reperfusion injury which is routinely managed with lidocaine. Attention has, therefore, focused on the suppression of the neutrophil respiratory burst with a therapeutic endpoint. The widest application of lidocaine remains in local analgesia. METHODS: A standard chemiluminescence technique was used to assess the human neutrophil leukocyte response to increasing doses of lidocaine in the presence or absence of particulate hydroxyapatite. RESULTS: No reduction of oxygen radical production was seen at the drug concentration of 1 mg/ml. A clear, concentration-dependent inhibition was seen at 2 mg/ml, 3 mg/ml, 4 mg/ml and 8 mg/ml concentrations. These drug concentrations may be reached at or near the site of injection in local anaesthetic use. CONCLUSION: Lidocaine showed profound anti-inflammatory action in this experimental system. Controlled studies in the clinical setting would identify the optimal analgesic and anti-inflammatory dosage, whilst preserving host defence without compromising tissue repair.

Functional integrity of human neutrophils following 24 hour incubation with hydroxyapatite and fluoride.

We have previously shown that hydroxyapatite (HA) priming of human neutrophils to a second stimulus of formyl-methionyl-leucyl-phenylalanine (fMPL) is influenced by a bisphosphonate and fluoride. The purpose of this study was to investigate the long-term effects of low concentrations of NaF (10(-3)-10(-11) mol/LF) on HA-mediated neutrophil chemiluminescence (CL) as a measure of oxidative function. CL assays were conducted following extended time periods of incubation (30 min, 3 h, 18 h and 24 h). Results were calculated as integrals of total energy output and expressed as the difference between the experimental (NaF/HA) and control (cells alone) assays. Transmission electron microscopy (TEM) was used to estimate cellular integrity and confirm HA phagocytosis. CL inhibition was observed at all fluoride concentrations at 30 min incubation. No significant difference compared to the control was observed in the CL output at 3 or 18 h. However, at 24 h the response showed a significant increase in activity at all NaF concentrations. The TEM results confirmed the functional integrity of the neutrophils, particularly those phagocytosing HA particles up to 24 h. Based on these results we demonstrate that human peripheral blood neutrophils can be maintained in a fully functional state with respect to the respiratory burst and morphology for at least 24 h.

The comparative clinical efficacy of pyrophosphate/triclosan, copolymer/triclosan and zinc citrate/triclosan dentifrices for the reduction of supragingival calculus formation.

Three triclosan-containing "multi-benefit" dentifrices were compared for clinical efficacy in reducing supragingival calculus formation following a dental prophylaxis. A total of 544 subjects completed a double-blind parallel-group clinical study using the Volpe-Manhold Index (VMI) to record severity and occurrence of supragingival calculus. The study design included a pre-test period where the calculus formation rate was measured in subjects brushing with a placebo dentifrice. Following a prophylaxis, subjects were stratified for age, gender and VMI scores and assigned to one of four treatments: 1) a dentifrice containing 5.0% soluble pyrophosphate/0.145% fluoride as NaF/silica abrasive/0.28% triclosan (hereafter PPi/TCS-comparable to Crest Complete dentifrice, Procter & Gamble, UK); 2) a commercial dentifrice containing 2.0% Gantrez acid copolymer/ 0.145% fluoride as NaF/silica abrasive/0.30% triclosan (hereafter Gan/TCS-Colgate Total dentifrice, Colgate-Palmolive Company, UK); 3) a commercial dentifrice containing 0.5% zinc citrate trihydrate/0.15% fluoride as sodium monofluorophosphate/silica abrasive/0.20% triclosan (hereafter Zn/TCS-Mentadent P dentifrice, Unilever, UK); and 4) a control dentifrice comprised of 0.145% fluoride as NaF/silica abrasive (hereafter Control). Subjects were instructed to use their assigned dentifrice at least twice per day and to brush as they do normally. Supragingival calculus formation was assesed at two and four months using site-specific and whole-mouth VMI indices for both calculus severity and occurrence. Following four months of use, the PPi/TCS dentifrice provided statistically significant reductions in calculus severity (22-23%) and occurrence (15%) as compared with the Control dentifrice. The Zn/TCS dentifrice also provided significant reductions in calculus severity (17-19%) and occurrence (12-13%) as compared with the Control. The Gan/TCS produced no statistically significant reductions in calculus formation (occurrence or severity) compared with the Control. The PPi/TCS dentifrice provided statistically significant reductions in calculus severity (15-21%) and occurrence (12-16%) as compared with the Gan/TCS dentifrice. These results support the clinical effectiveness of PPi/TCS and Zn/TCS dentifrices for the reduction of supragingival dental calculus formation following a dental prophylaxis.

Influence of heat inactivation of human serum on the opsonization of Streptococcus mutans.

Phagocytosis of bacteria, such as Streptococcus mutans, is important to host defense. One mechanism by which phagocytosis can be enhanced is by antibody or complement-mediated opsonization of bacteria. Many studies utilize opsonization of bacteria to enhance a cellular response, but little information has been found examining methodology or validity of the opsonization process following the denaturization of the serum. Human serum was inactivated by heat in order to disrupt the classical and alternative pathways of the complement cascade. S. mutans isolated from human subjects were opsonized with heat-inactivated human serum before exposing them to viable neutrophils in vitro. Luminol-dependent chemiluminescence (CL) was used to measure neutrophil activation. Human serum used to opsonize the bacteria was denatured by incubation at 57 degrees C for intervals of 30 and 60 min to inactivate complement. The results from the opsonization data indicated that there was significantly increased CL with 60-min inactivation of the serum (34% increase in mean integration mV.min; p < or = 0.05) over the nonopsonized control. This indicated a successful opsonization of the bacteria. In addition, the data demonstrate that the inactivation of serum requires a minimum of 60 min at 57 degrees C to disrupt the complement cascade, while 30- and 15-min inactivations produced no significant increase in CL activity over the control. Standard sandwich ELISA assays, detecting complement binding to S. mutans, confirmed successful heat inactivation of serum showing a significant decrease (p < or = 0.001) in complement binding to S. mutans after 30 min, but could not explain the increased CL response after 60-min heat deactivation of the serum.

Activation of the neutrophil respiratory burst requires both intracellular and extracellular calcium.

Activation of neutrophil oxidases, including NADPH oxidase, is Ca2+ dependent. The aim of this study was to determine the roles of intra- and extracellular Ca2+, leading to generation of the respiratory burst, as monitored by luminol-dependent chemiluminescence (CL). All results were recorded as integrals (millivolt.min) and compared by a two-tail Student's t test. Preincubation of cells with chelators of intra- or extracellular Ca2+ inhibited N-Formyl-Met-Leu-Phe (FMLP)-stimulated burst activity (p < 0.01). In contrast, stimulation by phorbol myristate acetate (PMA), while inhibited by extracellular Ca2+ chelation with EGTA (p < 0.001), was potentiated by intracellular Ca2+ chelation with BAPTA (p < 0.01). This suggests that the protein kinase C (PKC)-mediated burst may be diminished by intracellular Ca(2+)-dependent phosphatase. A selective inhibitor of tyrosine phosphatase, sodium vanadate, potentiated CL generation by both FMLP and PMA, indicating a dominant phosphatase activation with transiently increased Ca2+, masking the kinase-mediated respiratory burst. The selective inhibitors of PKC or tyrosine kinase prevented PMA and vanadate/PMA stimulation (p < 0.005). Furthermore, the putative Ca2+ channel agonists glutamate (10(-5)M) and N-methyl-D-aspartate (NMDA) (10(-5)M) alone failed to influence CL output, but produced marked potentiation following pre-treatment with vanadate. Again this indicates a dominant activation of phosphatase triggered by the glutamate-mediated Ca2+ influx, so masking the kinase-dependent NADPH oxidase activity. A competitive antagonist of NMDA, AP7, significantly decreased vanadate-mediated CL in an EGTA-sensitive manner (p < 0.001). The data confirm a requirement for intra- and extracellular Ca2+ in neutrophil respiratory burst activation via the kinase/phosphatase cycle, and an agonist effect by NMDA within the Ca2+ cascade mechanism.

Human gingival crevicular fluid keratin at healthy, chronic gingivitis and chronic adult periodontitis sites.

The present study was designed to determine, in a cross-sectional study, whether there was any relationship between the keratin-positive material in gingival crevicular fluid and the clinical periodontal status. Keratins were selected as putative indicators of degradation of epithelial cells cytoskeletal proteins. Keratin positive material was determined by enzyme-linked immunosorbent assay in 42 subjects exhibiting clinical sites of health, chronic gingivitis and chronic periodontitis. The concentration of keratin in parotid saliva was also measured for each subject. Keratin concentration in gingival crevicular fluid samples was significantly greater at sites exhibiting signs of gingivitis and periodontitis compared with healthy sites. No differences were detected between sites exhibiting gingivitis and periodontitis. No differences were found between the 3 groups for the saliva keratin-positive material which was significantly less than that detected in gingival crevicular fluid. These results suggest that gingival crevicular fluid keratin concentration may serve as a marker of gingival damage.

Helicobacter pylori infection and dental care.

Sixty two patients (mean age 45.6 years) were assessed for oral hygiene and periodontal disease by dental examination before endoscopy. Information about oral care, smoking, and dentures was obtained and samples of dental plaque collected. The presence of Helicobacter pylori in plaque as sought by culture and polymerase chain reaction (PCR), and gastric antral biopsy specimens were taken for histological examination. Although H pylori was detected in the antral specimens of 34 patients (54%) all of the cultures of dental plaque were negative, and PCR was only positive from the dentures of one patient. Smokers had poor oral hygiene, visited their dentist less often, and brushed their teeth less frequently. There was no correlation of H pylori gastritis with either dental hygiene or periodontal disease. These results suggest that dental plaque or dentures are not an important reservoir for H pylori and are probably not a significant factor in transmission of the organism. The conflicting results in published works may be caused by differences in sample collection, culture techniques, or oral contamination from gastric juice as a result of gastro-oesophageal reflux at the time of endoscopy.

Modification by clodronate and fluoride of hydroxyapatite-induced neutrophil chemiluminescence in vitro.

In the light of previous studies demonstrating an inhibition of oxidative metabolism in human neutrophil granulocytes by the bisphosphonate, clodronate, and considerable evidence of oxidative pathway stimulation by fluoride, the aim of this study was to determine the combined effect of these two agents. A luminol-dependent, fMLP stimulated chemiluminescence system was used and showed that 10(-3) M fluoride significantly increased the inhibitory effect of clodronate (3 ug/ml and 10 ug/ml) when bound to particulate hydroxyapatite (HA), phagocytosed by the neutrophils. By contrast, 10(-4) M fluoride appeared to counteract this inhibition and was subsequently shown, following more prolonged incubation within the cell model system, to significantly enhance cellular oxidative activity by 25% compared to the HA/clodronate control. It is likely that the kinetics of clodronate and fluoride follow a different time course and their intracellular target receptors differ, but the cellular model employed may help to elucidate more precisely the basis of their therapeutic use in bone diseases.