Increased risk for tooth extraction in primary hyperparathyroidism and hypercalcemia: a population study.

The aim of this study was to analyze dental comorbidities in untreated primary hyperparathyroidism (pHPT). Patients with pHPT subjected to parathyroidectomy (PTX) at Karolinska University Hospital, Stockholm, during 2011-2016 (n = 982) were selected from the Scandinavian Quality Register of Thyroid, Parathyroid and Adrenal surgery and compared to a general population cohort (n = 2944), matched for age and gender. Dental data was obtained from the Swedish Dental Health Registry for the 3 years prior to PTX. The incidence rate ratios (IRRs) of tooth loss by extraction, periodontal interventions, and dental visit rate were analyzed by Poisson regression models. In order to analyze the impact of disease severity, the PHPT cohort was sub-grouped based on preoperative serum levels of ionized calcium (S-Ca2+). The total number of tooth extractions, periodontal interventions, and number of visits were similar in the cohorts. PHPT patients belonging to the quartile with the highest S-Ca2+ (≥ 1.51 mmol/L) had increased risk for tooth extraction (IRR 1.85; 95% CI 1.39-2.46). Female gender independently amplified the risk (IRR 1.341, P < 0.027). This study indicates an association between pHPT and oral disorders reflected by increased tooth loss by extraction related to high S-Ca2. Increased awareness of dental comorbidity in primary hyperparathyroidism may benefit a large group of patients with a common disease through earlier detection and prevention.

A long-term follow-up study on the natural course of oral leukoplakia in a Swedish population-based sample.

AIM: To assess the natural course of screening-detected oral leukoplakia (OL) among non-consulting individuals. METHODS: A cohort of 555 individuals with OL, confirmed in 1973-1974 during a population-based survey, were followed through January 2002 via record linkages with nationwide and essentially complete registers. A sample of 104 drawn from the 297 surviving cohort members who still were living in the area in 1993-1995 was invited to a re-examination. Sixty-seven of them attended. RESULTS: At the time of re-examination OL had disappeared in 29 (43%) individuals. There was a statistically significant association between cessation of/no smoking habits in 1993-1995 and the disappearance of OL. Never/previous daily smokers were thus over-represented among individuals whose OL had disappeared compared to those with persisting OL [n = 23 (82%) vs. n = 18 (47%), P < 0.01]. Eighteen (78%) of the twenty three non-smokers with disappearing OL had quit after the initial examination. One man and two women developed oral cancer during follow-up while 0.7 and 0.07, respectively, were expected. CONCLUSION: Smoking cessation was associated with an increased disappearance of OL. Hence, at least one-fourth had lesions that could be classified as tobacco-related. Small observed and expected numbers prohibited firm conclusions about a possible excess risk of developing oral cancer.

On the natural course of oral lichen lesions in a Swedish population-based sample.

OBJECTIVES: The aim was to assess the natural course of oral lichen lesions (OLL) among unselected, non-consulting individuals. SUBJECTS AND METHODS: A cohort of 327 subjects with OLL, confirmed in 1973-1974 during a population-based survey in two Swedish municipalities, was followed through January 2002 via record linkages with nationwide and essentially complete registers. A sample of 80 drawn from the 194 surviving subjects who still resided in the area in 1993-1995 was invited for interview and oral re-examination. RESULTS: At the end of follow-up, one case of oral cancer was detected, while 0.4 were expected. The overall mortality among subjects with OLL was not significantly different from that in the 15,817 OLL-free subjects who participated in the initial population based survey in 1973-1974. The lesion had disappeared in 14 (39%) of 36 re-examined subjects with white OLLs in 1973-1974, and four (11%) had transformed into red types. In the corresponding group of 19 with red forms initially, five (26%) had become lesion free and four (21%) had switched to white types. Although the cohort size does not permit firm conclusions regarding oral cancer risk, the natural course over up to 30 years appears to be benign in the great majority.

Mercury exposure in utero and during infancy.

Mercury in blood samples was speicated from mothers and their infants up to 2 mo after delivery. There were significant correlations between umbilical cord blood and maternal blood for methylmercury (MeHg) and inorganic mercury (I-Hg) levels. The MeHg levels in cord blood were significantly higher than in maternal blood, while I-Hg levels were significantly higher than in maternal blood, while I-Hg levels were about the same. The maternal MeHg and I-Hg levels remained stable during the sampling period, whereas the MeHg concentration in infant blood decreased more than 45% between the 72-h and 2 mo sampling times. The I-Hg levels in infant blood were low at birth, and remained low during the sampling period. The results of the present study do not support I-Hg absorption through milk as a significant source of exposure. However, the number of observations is small, and a larger study is warranted in order to verify the data.

Mercury uptake and kinetics after ingestion of dental amalgam.

The aim of the present study was to investigate the G-1 uptake of mercury (Hg) after intake of a single dose of amalgam-Hg, followed by pharmacokinetic analysis of the data. Eleven volunteers without amalgam fillings ingested 1.00 g amalgam powder. Hg in plasma vs. time was analyzed with a two-compartment model by means of mixed-effects modeling. A fraction of the absorption rate of Hg to the central compartment was inversely proportional to the plasma ferritin levels. The population mean half-life of the terminal phase of Hg in plasma was 37 days, with a considerable standard deviation in the population. The absorbed fraction of the administered dose was estimated to be about 0.04%. It is concluded that the G-1 uptake of Hg is of quantitative importance during dental treatment.

A compartmental model for the kinetics of mercury vapor in humans.

In an earlier study, we exposed nine healthy volunteers to known concentrations of mercury (Hg) vapor in air (median 399; range 365-430 micrograms/m3) for 15 min during light physical exercise (50 W) (Sandborgh-Englund, G., et al., Toxicol. Appl. Pharmacol. 150, 146-153, 1998). Exhaled air, urine, and plasma samples were collected. In the present study, the experimental observations from eight of these volunteers were subjected to an analysis with the aid of the software NONMEM. A four-compartment model, including two depot compartments to account for retention in lungs and kidneys, respectively, gave the best fit to the data. The fraction of dose excreted from the central compartment directly into urine was found to be positively correlated with the preexposure excretion rate of Hg via urine. The median half time in the respiratory depot compartment was estimated to 1.81 days (range 1.60-1.92). The median half time in the excretion depot was estimated to 63.2 days (range 12.8-98.9). The model was tested by simulating two experiments found in the literature and agreed well with these older data sets. Further simulations indicated that the excretion of Hg via urine would not reach a plateau until several months postexposure for most subjects.

Acute exposure to mercury from amalgam: no short-time effect on the peripheral blood lymphocytes in healthy individuals.

Mercury, released from dental amalgam, has been considered to adversely affect the human immune system. This study has been performed in order to evaluate if an acute low-dose mercury exposure, achieved by total amalgam removal in 10 healthy individuals, would affect the immunocompetent cells in human blood when the mercury level in blood and plasma was increasing. Induction of lymphocyte proliferation, measured as spontaneous de novo DNA synthesis, and total T cells, CD4+ T cells, CD8+ T cells, and B cells, was studied prior to and 7, 31, and 48 h after amalgam removal. In addition, the levels of interleukin-6 (IL-6) and C-reactive protein (CRP) in serum/plasma were measured. Despite a significant increase of the plasma mercury levels within 24 h after intervention, no significant influence on the peripheral blood lymphocytes could be detected during the first 48 h. The serum IL-6 levels increased significantly within 48 h after intervention, but were still low and within normal range. No influence on the CRP levels up to 7 d after amalgam removal was detected.

The absorption, blood levels, and excretion of mercury after a single dose of mercury vapor in humans.

Nine healthy volunteers without amalgam fillings were exposed to 400 micrograms/m3 mercury vapor (Hg0) for 15 min, corresponding to 5.5 nmol Hg0/kg body wt (median range: 4.4-7.2). Frequent sampling of blood, urine, and exhaled air was performed for 30 days after exposure. The median retention of Hg0 was 69% of the inhaled dose. During the first 3 days after exposure 7.5-12% of the absorbed dose was lost by exhalation, with the median half time of Hg0 in expired breath being 2.0 days. In blood and plasma, a rapid absorption phase of Hg was seen, followed by a biexponential decline of the curves in both media. A substantial interindividual variation was observed in the area under the concentration-time curves of Hg in blood and plasma. In plasma the median half time of the second phase was 10 days. About 1.0% of the absorbed Hg was excreted via urine during the first 3 days after exposure, whereas the estimated amount excreted during 30 days ranged from 8 to 40%. In order to evaluate the chronic exposure to mercury from dental amalgam in the general population, the daily Hg dose from the fillings were estimated based on the plasma Hg levels found in subjects with amalgam fillings and on the plasma Hg clearance obtained in the present study. The daily Hg dose was estimated to 5-9 micrograms/day in subjects with an ordinary number of amalgam fillings.

Determination of low levels of total mercury in blood and plasma by cold vapour atomic fluorescence spectrometry.

A sensitive and semi-automated analytical method allowing determination of low and normal levels of total mercury in human blood and plasma using cold vapour atomic fluorescence is described. Samples are digested overnight, or at an elevated temperature for 4 h, followed by bromination at room temperature. After reduction with tin (II), analysis is performed using automated continuous flow vapour generation coupled to a fluorescence detector, allowing 20 samples to be analysed per hour. Detection limits for blood and plasma were found to be 0.9 and 0.5 nmol Hg l-1, respectively. The method precision at various concentrations of mercury was determined. For whole blood at 8.1 nmol Hg l-1 and 12.9 nmol Hg l-1, the within-day precision was 5% and 6% and the between-day precision 9% and 6%, respectively. For plasma at 1.3 nmol Hg l-1, the within-day precision was 13% while the between-day precision was 17%. Accuracy was evaluated by an inter-laboratory comparison study. At blood mercury concentrations below 60 nmol Hg l-1 the results from the current method were almost identical to those obtained with radiochemical neutron activation analysis, commonly regarded as a reference method. The present method should have merits in relation to previously used methods using atomic absorption spectrometry.

Toxicological aspects on the release and systemic uptake of mercury from dental amalgam.

This paper summarizes some recent reports on mercury release from amalgam fillings and resulting concentrations in biological fluids, development of antibiotic resistance, and kidney function. In a series of studies of subjects with amalgam fillings, mercury (Hg) levels were followed in saliva, feces, blood, plasma, and urine before and until 60 d after removal of all of the fillings. The Hg concentrations in saliva remained elevated for at least 1 wk, suggesting that dissolved Hg vapor is not the major source of mercury in mixed saliva. An absorption phase of Hg was seen in plasma during 24 h after amalgam removal. After 60 d the plasma Hg concentration was reduced to 40%, of the baseline level. The decrease per amalgam surface was 0.11 nmol/l (range 0.02 0.40). The Hg level in feces increased two orders of magnitude two days after amalgam removal. At day 60, the median Hg concentration was still slightly higher than the median value of the amalgam free control group. The resistance patterns of the oral and intestinal microflora in these subjects were also studied. In the intestinal microflora, the relative amount of intestinal microorganisms resistant to 50 microM HgCl2 peaked 7 d after removal of the amalgam fillings, with a median value per sample of 6.1%, compared to 1.3% in samples collected prior to the Hg exposure. However, no statistical differences in the resistance pattern of the oral microflora were detected between the control and the experimental groups. A number of sensitive kidney function parameters were measured 1 wk before and 1, 2, and 60 d after amalgam removal. No effects on the various kidney parameters studied were recorded. According to the conclusions of independent evaluations from different state health agencies, the release of mercury from dental amalgam does not present any non-acceptable risk to the general population.

Mercury in biological fluids after amalgam removal.

Dental amalgam is the major source of inorganic mercury (Hg) exposure in the general population. The objective of the present study was to obtain data on changes in Hg levels in blood, plasma, and urine following removal of all amalgam fillings during one dental session in 12 healthy subjects. The mean number of amalgam surfaces was 18 (range, 13 to 34). Frequent blood sampling and 24-hour urine collections were performed up to 115 days after amalgam removal, and in eight subjects additional samples of plasma and urine were collected up to three years after amalgam removal. A transient increase of Hg concentrations in blood and plasma was observed within 48 hours after amalgam removal. In plasma, the peak concentrations significantly exceeded the pre-removal plasma Hg levels by, on average, 32% (1.3 nmol/L; range, 0.1 to 4.2). No increase in the urinary Hg excretion rate was apparent after amalgam removal. An exponential decline of Hg was seen in all media. Sixty days after the amalgam removal, the Hg levels in blood, plasma, and urine had declined to approximately 60% of the pre-removal levels. In seven subjects, who were followed for up to three years, the half-lives of Hg in plasma and urine were calculated. In plasma, a bi-exponential model was applied, and the half-life was estimated at median 88 days (range, 21 to 121). The kinetics of Hg in urine (nmol/24 hrs) fit a mono-exponential model with a median half-life of 46 days (range, 35 to 67). It is concluded that the process of removing amalgam fillings can have a considerable impact on Hg levels in biological fluids. After removal, there was a considerable decline in the Hg levels of blood, plasma, and urine, which slowly approached those of subjects without any history of amalgam fillings.

A multidisciplinary clinical study of patients suffering from illness associated with release of mercury from dental restorations. Medical and odontological aspects.

OBJECTIVE: To describe medical and odontological aspects of patients who believed their illness was caused by mercury in dental fillings. DESIGN: Comparison of self-reported and assessed medical and odontological variables. SETTING: The School of Dentistry, Karolinska Institute. SUBJECTS: Sixty-seven patients, referred for suspected side-effects of mercury in dental fillings, and 64 matched controls. MAIN OUTCOME MEASURES: Incidence of medical and odontological diagnoses, own perception of health, and incidence of self-reported symptoms. RESULTS: Three quarters of the patients were women. The mean age was 49 years. Thirty-seven patients (55%) and 47 controls (73%) (NS) showed no sign of somatic disease. Half of the patients felt ill or very ill at the time of the examination. Patients reported twice as many symptoms as the controls during a 3-month period. Patients reported a higher prevalence of very low resting saliva secretion rate, and a higher number of decayed tooth surfaces and of instances of temporomandibular joint dysfunction. CONCLUSION: Patients' feelings of ill-health were more likely related to psychiatric than somatic diagnoses. This study underlines the importance of making an overall diagnosis, including both mental and somatic disorders, especially in unclear cases and in self-diagnosed illnesses.

Mercury in saliva and feces after removal of amalgam fillings.

The toxicological consequences of exposure to mercury (Hg) from dental amalgam fillings is a matter of debate in several countries. The purpose of this study was to obtain data on Hg concentrations in saliva and feces before and after removal of dental amalgam fillings. In addition Hg concentrations in urine, blood, and plasma were determined. Ten subjects had all amalgam fillings removed at one dental session. Before removal, the median Hg concentration in feces was more than 10 times higher than in samples from an amalgam free reference group consisting of 10 individuals (2.7 vs 0.23 mumol Hg/kg dry weight, p < 0.001). A considerable increase of the Hg concentration in feces 2 days after amalgam removal (median 280 mumol Hg/kg dry weight) was followed by a significant decrease. Sixty days after removal the median Hg concentration was still slightly higher than in samples from the reference group. In plasma, the median Hg concentration was 4 nmol/liter at baseline. Two days after removal the median Hg concentration in plasma was increased to 5 nmol/liter and declined subsequently to 1.3 nmol/liter by Day 60. In saliva, there was an exponential decline in the Hg concentration during the first 2 weeks after amalgam removal (t 1/2 = 1.8 days). It was concluded that amalgam fillings are a significant source of Hg in saliva and feces. Hg levels in all media decrease considerably after amalgam removal. The uptake of amalgam mercury in the GI tract in conjunction with removal of amalgam fillings seems to be low.

A multidisciplinary clinical study of patients suffering from illness associated with mercury release from dental restorations: psychiatric aspects.

The aim of this study was to map the psychological/psychiatric, odontological and medical aspects of patients with symptoms allegedly related to the side-effects of mercury in dental fillings. A total of 67 consecutive patients and 64 controls matched for age, sex and residential area were included in the study. The most striking result was the high prevalence of psychiatric disorders in the patients (89%) compared to the controls (6%), predominantly somatoform disorders. The personality traits differentiating the patients according to the Karolinska Scales of Personality (KSP) were somatic anxiety, muscular tension, psychasthenia and low socialization. More patients than controls showed alexithymic traits. The prevalence of diagnosed somatic diseases was higher, but not sufficiently so to explain the large difference in perceived health. The multiple symptoms and signs of distress displayed by the patients could not be explained either by the odontological data or by the medical examination. Our data indicate that the patients show sociodemographic and clinical patterns similar to those of somatizing patients. The medicalization of the suffering of these patients and the neglect of psychiatric problems prevent the use of appropriate psychotherapeutic approaches.

No evidence of renal toxicity from amalgam fillings.

Dental amalgam continuously releases mercury. Studies of sheep [Boyd et al., Am. J. Physiol. 261 (Regulatory Integrative Comp. Physiol. 30): R1010-R1014, 1991] showed decreased renal function after placement of amalgam fillings. In this study, renal function was investigated in 10 healthy volunteers before and after amalgam removal. The subjects had an average of 18 tooth surfaces filled with amalgam, which was removed during one dental session. One week before and sixty days after removal, the glomerular filtration rate (GFR) was determined by 51Cr-EDTA clearance technique. Blood and urine samples were collected for analysis of mercury, creatinine, beta 2-microglobulin, N-acetyl-beta-glucosaminidase (NAG), and albumin 1 wk before and 1, 2, and 60 days after amalgam removal. The plasma mercury concentration increased significantly 1 day after removal. Sixty days later, significantly lower mercury levels were found in blood, plasma, and urine. The GFR values were similar before and after mercury exposure (mean 94 and 94 ml/min per 1.73 m2, respectively). No detectable effects occurred on excretion of NAG, beta 2-microglobulin, or albumin. It is concluded that no signs of renal toxicity could be found in conjunction with mercury released from amalgam fillings.

Resistance of the normal human microflora to mercury and antimicrobials after exposure to mercury from dental amalgam fillings.

The concentrations of mercury in saliva and feces and the resistance pattern of the gastrointestinal microflora were investigated for 20 subjects. Ten patients, with a mean number of 19 amalgam surfaces, had all amalgam fillings removed during one dental session. Ten subjects without amalgam fillings served as a control group. Saliva and fecal samples were collected before amalgam removal and 2, 7, 14, and 60 days afterward. Mercury levels in saliva and feces correlated significantly with the number of amalgam surfaces. No differences in the resistance pattern of the oral microflora were detected between the two groups. In the amalgam group there was an increase in the relative number of intestinal microorganisms resistant to mercury, ampicillin, cefoxitin, erythromycin, and clindamycin on days 7-14. This was not statistically significant in light of the normal variations of the control group. A significant correlation between the prevalence of mercury resistance and multiple antimicrobial resistance in intestinal bacterial strains was observed.

DMSA administration to patients with alleged mercury poisoning from dental amalgams: a placebo-controlled study.

The present investigation was performed to determine the effect of 14-day oral administration of meso-2.3-dimercaptosuccinic acid (DMSA) on the urinary mercury excretion and the potential reduction of blood and plasma mercury concentrations, and also to relate these effects to possible decrease of symptoms, allegedly associated with amalgam fillings. Twenty subjects, relating their symptoms to mercury from amalgam fillings, received 20 mg/kg DMSA or placebo for 14 days. Their symptoms and mood states were recorded during the study and at a check-up 3 months later. Interpretation was based on intra-individual differences. DMSA-treatment resulted in an average increase in urinary mercury excretion by 65% and a decrease in blood mercury levels of 0.04 microgram/L/day. At the check-up after 3 months, urinary mercury excretion had returned to the pre-treatment level. No treatment effect of DMSA was apparent on subjective symptoms and mood state. One statistically significant treatment effect was noted-a decrease in fatigue-inertia in the DMSA-group-but there was no demonstrable correlation with increased urinary excretion or decreased blood concentration of mercury. Three subjects showed hypersensitive reactions, probably DMSA-specific, at the end of the treatment period. This placebo-controlled study provides no scientific support for diagnostic or therapeutic administration of DMSA for symptoms allegedly associated with chronic mercury exposition from dental amalgam fillings.