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Biomedical subjects

E A Krall

Publications and source records attributed to E A Krall.

At least 19 recordsLinked to original sources

Selective and nonselective cyclooxygenase-2 inhibitors and experimental fracture-healing. Reversibility of effects after short-term treatment.

BACKGROUND: Cyclooxygenase-2-specific anti-inflammatory drugs (coxibs) and nonspecific nonsteroidal anti-inflammatory drugs have been shown to inhibit experimental fracture-healing. The present study tested the hypothesis that these effects are reversible after short-term treatment. METHODS: With use of a standard model of fracture-healing, identical ED50 dosages of either a nonsteroidal anti-inflammatory drug (ketorolac), a coxib (valdecoxib), or vehicle (control) were orally administered to rats for either seven or twenty-one days and fracture-healing was assessed with biomechanical, histological, and biochemical analyses. RESULTS: When healing was assessed at twenty-one days, the seven-day treatment produced only a trend for a higher rate of nonunion in valdecoxib and ketorolac-treated animals as compared with controls. No differences were observed at thirty-five days. The twenty-one-day treatment produced significantly more nonunions in valdecoxib-treated animals as compared with either ketorolac-treated or control animals (p < 0.05), but these differences disappeared by thirty-five days. The dose-specific inhibition of these drugs on prostaglandin E2 levels and the reversibility of the effects after drug withdrawal were assessed in fracture calluses and showed that ketorolac treatment led to twofold to threefold lower levels of prostaglandin E2 than did valdecoxib. Withdrawal of either drug after six days led to a twofold rebound in these levels by fourteen days. Histological analysis showed delayed remodeling of calcified cartilage and reduced bone formation in association with valdecoxib treatment. CONCLUSIONS: Cyclooxygenase-2-specific drugs inhibit fracture-healing more than nonspecific nonsteroidal anti-inflammatory drugs, and the magnitude of the effect is related to the duration of treatment. However, after the discontinuation of treatment, prostaglandin E2 levels are gradually restored and the regain of strength returns to levels similar to control.

Animals↗

Cigarette smoking increases the risk of root canal treatment.

Few studies have investigated smoking as a risk factor for root canal treatment. We studied the effect of smoking on the incidence of root canal treatment, controlling for recognized risk factors, in 811 dentate male participants in the VA Dental Longitudinal Study. Participants were not VA patients. Follow-up ranged from 2 to 28 years. Root canal treatment was verified on radiographs and evaluated with proportional hazards regression models. Compared with never-smokers, current cigarette smokers were 1.7 times as likely to have root canal treatment (p < 0.001), but cigar and/or pipe use was not significantly associated with root canal treatment. The risk among cigarette smokers increased with more years of exposure and decreased with length of abstinence. These findings suggest that there is a dose-response relationship between cigarette smoking and the risk of root canal treatment.

Adult↗

Lesions of endodontic origin and risk of coronary heart disease.

A paucity of epidemiologic research exists regarding systemic health consequences of endodontic disease. This study evaluated whether incident radiographically evident lesions of endodontic origin were related to development of coronary heart disease (CHD) among 708 male participants in the VA Dental Longitudinal Study. At baseline and every three years for up to 32 years, participants (who were not VA patients) received complete medical and dental examinations, including full-mouth radiographs. Cox regression models estimated the relationship between incident lesions of endodontic origin and time to CHD diagnosis. Among those < or = 40 years old, incident lesions of endodontic origin were significantly associated with time to CHD diagnosis (p < 0.05), after adjustment for covariates of interest, with hazard ratios decreasing as age increased. Among those > 40 years old, no statistically significant association was observed. These findings are consistent with research that suggests relationships between chronic periodontal inflammation and the development of CHD, especially among younger men.

Adult↗

Efficacy of periodontal disease and tooth loss to screen for low bone mineral density in Japanese women.

The relationship between oral indicators and bone mineral density (BMD) has been studied by many investigators, with mixed and complex results. The purpose of the present cross-sectional study was to evaluate the associations of periodontal conditions and tooth loss with metacarpal BMD (m-BMD) in a community-based cohort and the usefulness of tooth count as a potential screening tool to detect low BMD. Subjects were 356 Japanese women (171 premenopausal, mean age 37.9+/-8.0 years; 185 postmenopausal, mean age 63.3+/-7.7 years). Periodontal status was evaluated by the Community Periodontal Index of Treatment Needs (CPITN). m-BMD was measured by computerized X-ray densitometry. The proportion of subjects with periodontitis (CPITN 3 or 4) increased as m-BMD decreased. The odds ratio (OR) of osteopenia or osteoporosis in relation to periodontitis was 3.2 (95% confidence interval [CI], 2.0--5.3). After adjustment for age and menopausal status, the OR was 2.0 (95% CI, 1.1--3.7). Among postmenopausal women, those having fewer than 20 teeth were 1.6 times more likely to have low m-BMD than those having more than 20 teeth (chi-square for trend in postmenopausal group, 4.27; P<0.05). Receiver-operating curve (ROC) analysis indicated that number of teeth remaining or CPITN score had a greater than 50/50 chance to correctly identify women with osteoporosis or osteopenia, but the areas under the curve (0.72 and 0.67, respectively) are considered less than highly accurate screening tools. These results indicate that periodontitis and tooth loss after menopause may be useful indicators of m-BMD loss in Japanese women.

Absorptiometry, Photon↗

Calcium and vitamin D supplements reduce tooth loss in the elderly.

PURPOSE: Oral bone and tooth loss are correlated with bone loss at nonoral sites. Calcium and vitamin D supplementation slow the rate of bone loss from various skeletal sites, but it is not known if intake of these nutrients affects oral bone and, in turn, tooth retention. SUBJECTS AND METHODS: Tooth loss was examined in 145 healthy subjects aged 65 years and older who completed a 3-year, randomized, placebo-controlled trial of the effect of calcium and vitamin D supplementation on bone loss from the hip, as well as a 2-year follow-up study after discontinuation of study supplements. Teeth were counted at 18 months and 5 years. A comprehensive oral examination at 5 years included assessment of caries, oral hygiene, and periodontal disease. The odds ratio (OR) and 95% confidence interval (CI) of tooth loss were estimated by stepwise multivariate logistic regression. Initial age (mean +/- SD) of subjects was 71 +/- 5 years, and the number of teeth remaining was 22 +/- 7. RESULTS: During the randomized trial, 11 of the 82 subjects (13%) taking supplements and 17 of the 63 subjects (27%) taking placebo lost one or more teeth (OR = 0.4; 95% CI: 0.2 to 0.9). During the 2-year follow-up period, 31 of the 77 subjects (40%) with total calcium intake of at least 1000 mg per day lost one or more teeth compared with 40 of the 68 subjects (59%) who consumed less (OR = 0.5; 95% CI: 0.2 to 0.9). CONCLUSION: These findings suggest that intake levels of calcium and vitamin D aimed at preventing osteoporosis have a beneficial effect on tooth retention.

Aged↗

Low metacarpal bone density, tooth loss, and periodontal disease in Japanese women.

The relationship between periodontitis and systemic bone mineral density in Japanese women is undetermined. We tested the hypothesis that periodontitis was more frequent in women with low metacarpal bone mineral density (m-BMD). Subjects were 190 Japanese women (89 premenopausal, 101 post-menopausal). Periodontal status was evaluated according to the Community Periodontal Index of Treatment Need (CPITN). M-BMD was measured by computed x-ray densitometry. The proportion of subjects with periodontitis (CPITN > or = 3) increased as m-BMD decreased in pre-menopausal (18.2%, 36.9%, and 66.6% in the normal, borderline, and very low m-BMD groups, p < 0.02) and post-menopausal women (41.5%, 54.8%, 60%, and 68.4% in the normal, borderline, low, and very low m-BMD groups, p < 0.05). Among post-menopausal women, those with very low m-BMD had fewer teeth present than women with normal m-BMD (19.9+/-7.2 vs. 25.1+/-4.1, p < 0.01). These results indicate that m-BMD loss is associated with periodontitis in Japanese women, and with tooth loss after menopause.

Adult↗

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.

Aged↗

Effect of withdrawal of calcium and vitamin D supplements on bone mass in elderly men and women.

BACKGROUND: Supplementation with calcium and vitamin D reduces bone loss and prevents fractures in elderly people, but it is not known whether any lasting benefit remains if the supplements are discontinued. OBJECTIVE: The objective was to determine whether gains in bone mineral density (BMD) induced by calcium and vitamin D supplementation persist after supplement withdrawal. DESIGN: Two-hundred ninety-five healthy, elderly men and women (aged >/=68 y) who had completed a 3-y randomized, placebo-controlled trial of calcium and vitamin D supplementation were followed for an additional 2 y during which no study supplements were given. BMD was measured by dual-energy X-ray absorptiometry, and biochemical variables related to calcium metabolism and bone turnover were measured. RESULTS: In the 128 men, supplement-induced increases in spinal and femoral neck BMD were lost within 2 y of supplement discontinuation, but small benefits in total-body BMD remained. In the 167 women, there were no lasting benefits in total-body BMD or at any bone site. Consistent with the observations on BMD, the bone turnover rates in both men and women (as measured by serum osteocalcin concentrations) returned to their original higher concentrations within the same 2-y period. CONCLUSION: Discontinued calcium and vitamin D supplementation has limited cumulative effect on bone mass in men and women aged >/=68 y.

Absorptiometry, Photon↗

Predictors of continued smoking over 25 years of follow-up in the normative aging study.

OBJECTIVES: This study tested the hypothesis that high daily cigarette consumption and addiction to smoking are risk factors for the long-term continuation of smoking. METHODS: Using longitudinal data from 986 male smokers, we entered cigarettes per day, psychological addiction, age, and education into a survival analysis as predictors of continued smoking over a 25-year period. RESULTS: Younger men and those who smoked more cigarettes per day were more likely to remain smokers in the long term. Addiction and education level were not significant predictors of continued smoking. CONCLUSIONS: Heavier smokers are more at risk than lighter smokers for long-term smoking. It is therefore very important to provide smoking cessation treatments for heavy smokers as early as possible after the initiation of smoking.

Adult↗

Smoking increases bone loss and decreases intestinal calcium absorption.

Cigarette use is a risk factor for increased bone mineral density (BMD) loss but the mechanisms are not well understood. The relationship of smoking to rates of BMD change at the femoral neck, spine, and total body, and to intestinal calcium absorption were examined in 402 elderly men and women (32 smokers, 370 nonsmokers) who participated in a 3-year placebo-controlled study of calcium and vitamin D supplementation. Subjects in the supplemented group took 500 mg/day of elemental calcium and 700 IU/day of cholecalciferol. Two-hour calcium absorption fraction was determined three times, at 18, 30, and 36 months, with a single isotope method utilizing 45Ca in a subset of 333 subjects. Annualized rates of BMD loss (adjusted for baseline BMD, weight, age, gender, supplementation status, and dietary calcium intake) were higher in smokers than nonsmokers at the femoral neck (-0.714 +/- 0.285 %/year vs. +0.038 +/- 0.084 %/year, p < 0.02), and total body (-0.360 +/- 0.101 %/year vs. -0. 152 +/- 0.030 %/year, p < 0.05). No significant difference was observed at the spine (+0.260 +/- 0.252 %/year in smokers vs. +0.593 +/- 0.074 %/year in nonsmokers, p = 0.21). The mean (+/- SEM) calcium absorption fraction was lower in smokers (12.9 +/- 0.8%, n = 23) than nonsmokers (14.6 +/- 0.2%, n = 310, p < 0.05) after adjustment for gender, age, supplementation status, and dietary calcium and vitamin D intakes. Smokers of at least 20 cigarettes per day (n = 15) had the lowest mean absorption fraction (12.1 +/- 1.1%). With calcium and vitamin D supplementation, the proportionate increase in urinary calcium/creatinine excretion was lower in smokers (44 +/- 12%) than nonsmokers (79 +/- 9%, p < 0.05). These results suggest that smoking accelerates bone loss from the femoral neck and total body in the elderly and that less efficient calcium absorption may be one contributing factor.

Aged↗

Alveolar bone loss and tooth loss in male cigar and pipe smokers.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. CLINICAL IMPLICATIONS: 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.

Adult↗

Periodontal disease and mortality from all causes in the VA Dental Longitudinal Study.

(The role that oral conditions may play as risk factors or indicators for various medical outcomes, including mortality, is not well understood. We have examined the relationship of periodontal disease to mortality from all causes in the VA Dental Longitudinal Study and Normative Aging Study, a prospective cohort study of the determinants of disease in aging men. Subjects were screened for entry into the closed-panel cohort in the mid-1960s, based on good medical health. They are not VA patients. We have used proportional hazards regression models to assess the relationship of periodontal health status at baseline to all-cause mortality over a 25+-year follow-up period. A total of 804 dentate subjects who were alive and medically healthy through their first follow-up exam were used in the analysis; of these, 166 died during subsequent follow-up through December 1996. Survival was calculated in years from baseline exam to death or censoring (most recent study examination date). To define periodontal health status at baseline, we separately used radiographic alveolar bone loss (ABL) (person-level scores of mean whole-mouth % ABL, measured with a Schei ruler using full-mouth series of periapical films) and periodontal clinical probing depths. Covariates included age at baseline, and assessments at baseline of smoking and alcohol use, education, body mass index, serum cholesterol, white blood cell count, blood pressure, family history of heart disease, and number of teeth present. We found that periodontal status at baseline was a significant and independent predictor of mortality in this cohort, while controlling for other recognized predictors in multivariate models. For each 20% increment in mean whole-mouth ABL, the subject's risk of death increased by 51% (RR = 1.51; 95% CI = 1.11-2.04). The increase in risk attributable to periodontal status was found to be similar in magnitude to, and independent of that attributable to cigarette smoking in this cohort. While the increased risk due to smoking was 1.52-fold (95% CI = 1.06-2.19), being in the population quintile with highest ABL scores (i.e., worst periodontal status) was associated with a 1.85 fold increase in risk (95% CI = 1.25-2.74) using multivariate analyses. The hypothesis that chronic oral infections, as in periodontitis, may have important systemic sequelae merits further investigation in prospective controlled studies.

Adult↗

Postmenopausal estrogen replacement and tooth retention.

Loss of underlying supportive alveolar bone is a major cause of tooth loss. Alveolar bone loss appears to be related to the status of the extracranial skeleton, and therapies that preserve skeletal bone may be expected to benefit tooth retention. An association between postmenopausal hormone replacement therapy (HRT) and tooth retention was found in a cohort of 488 elderly women, 72 to 95 years old, who participated in the Framingham Heart Study between 1948 and 1995. There was an association between duration of HRT and tooth retention for total number of teeth remaining and the individual types of teeth (incisors, canines, and premolars, but not molars) retained. The odds of being edentulous were reduced by 6% for each 1-year increase in duration of HRT use. The data suggest that postmenopausal HRT protects against tooth loss and reduces the risk of edentulism.

Age Factors↗

Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older.

BACKGROUND: Inadequate dietary intake of calcium and vitamin D may contribute to the high prevalence of osteoporosis among older persons. METHODS: We studied the effects of three years of dietary supplementation with calcium and vitamin D on bone mineral density, biochemical measures of bone metabolism, and the incidence of nonvertebral fractures in 176 men and 213 women 65 years of age or older who were living at home. They received either 500 mg of calcium plus 700 IU of vitamin D3 (cholecalciferol) per day or placebo. Bone mineral density was measured by dual-energy x-ray absorptiometry, blood and urine were analyzed every six months, and cases of nonvertebral fracture were ascertained by means of interviews and verified with use of hospital records. RESULTS: The mean (+/-SD) changes in bone mineral density in the calcium-vitamin D and placebo groups were as follows: femoral neck, +0.50+/-4.80 and -0.70+/-5.03 percent, respectively (P=0.02); spine,+2.12+/-4.06 and +1.22+/-4.25 percent (P=0.04); and total body, +0.06+/-1.83 and -1.09+/-1.71 percent (P<0.001). The difference between the calcium-vitamin D and placebo groups was significant at all skeletal sites after one year, but it was significant only for total-body bone mineral density in the second and third years. Of 37 subjects who had nonvertebral fractures, 26 were in the placebo group and 11 were in the calcium-vitamin D group (P=0.02). CONCLUSIONS: In men and women 65 years of age or older who are living in the community, dietary supplementation with calcium and vitamin D moderately reduced bone loss measured in the femoral neck, spine, and total body over the three-year study period and reduced the incidence of nonvertebral fractures.

Aged↗

Postmenopausal estrogen replacement and tooth retention.

PURPOSE: To determine if estrogen replacement therapy (ERT) is associated with improved tooth retention and lower risk of edentulism (no natural teeth remaining) in a cohort of elderly women. PATIENTS AND METHODS: Subjects were 488 women, aged 72 to 95, who participated in the 23rd examination cycle (1994 to 1995) of the Framingham Heart Study, a population-based study begun in 1948. The number of teeth remaining and their location were recorded by a trained observer. History and duration of ERT were obtained from records kept since cycle 10 (1960 to 1963). Third molars were excluded from all analyses. RESULTS: Women who ever used ERT were younger than nonusers by 1 year (80 +/- 4 years, n = 184, versus 81 +/- 4 years, n = 304, P = 0.019). Estrogen users had more teeth remaining than nonusers (12.5 +/- 0.8 versus 10.7 +/- 0.8 versus 10.7 +/- 0.6 teeth, P = 0.046, mean +/- SE) after controlling for age, smoking status, and education. Duration of estrogen use was an independent predictor of the number of teeth remaining (P = 0.015) such that each 4.2-year interval of use was associated with an increased mean retention of 1 tooth. Long-term estrogen users (more than 8 years, n = 48) had an average of 3.6 more teeth than women who never used estrogen (14.3 +/- 1.5 versus 10.7 +/- 0.6 teeth, P < 0.02). The association with duration of use was present among different types of teeth (incisors, canines, and premolars) but less strong for molars. The odds of being edentulous were reduced by 6% for each 1-year increase in duration of estrogen use (odds ratio = 0.94, P = 0.038, 95% confidence interval = 0.90 to 0.99). CONCLUSIONS: These data suggest that ERT protects against tooth loss and reduces the risk of edentulism. The associations of estrogen use and tooth retention are evident for all but the molars.

Age Factors↗

Bone mineral density and biochemical markers of bone turnover in healthy elderly men and women.

BACKGROUND: Osteoporosis risk in middle-aged women is twofold greater than that in men, and the difference increases with age. Gender differences in bone mineral density, estimated rates of bone loss, and usefulness of markers of bone metabolism for predicting bone density have not been well described in healthy elders aged 65 and above. The purpose of this cross-sectional analysis was to describe associations of bone mineral density at the hip, spine, and whole body with age, serum osteocalcin, and urinary N-telopeptide crosslinks of Type I collagen in healthy elderly men and women. METHODS: A total of 1,087 healthy adults (273 men and 814 women) aged 65 to 87 years were enrolled in a collaborative study at 3 sites: Tufts University (Boston, MA), University of Connecticut Health Center (Farmington, CT), and Creighton University (Omaha, NE). Bone mineral density (BMD) at three regions of the hip, the lumbar spine, and whole body was determined by dual-energy x-ray absorptiometry. Serum osteocalcin was measured by immunoassay, and measurement of N-telopeptide crosslinks (Ntx) in urine was made using an enzyme-linked radioimmunoassay (ELISA). RESULTS: Among women, the age-related decline in BMD at all non-spine skeletal sites was significantly different from zero, with the largest decline seen at the femoral neck (-.0038 g/cm2/y, p < .001) and the smallest at the trochanter of the hip (-.0023 g/cm2/y, p = .03). Among men, the changes at all non-spine sites were not significant. In both sexes, spine BMD tended to increase with age (men, +.0045 g/cm2/y, women, +.0003 g/cm2/y). Serum osteocalcin and urinary Ntx were inversely related to BMD at all skeletal sites, but the weakest associations were observed at the spine. Individuals whose values of both osteocalcin and Ntx were in the lowest quartiles of the respective sex-specific distributions had mean femoral neck BMD that were 11% higher than individuals with marker values in the highest quartiles. CONCLUSIONS: These findings suggest that age-related decreases in BMD may vary by gender and skeletal site. Determinations of osteocalcin and N-telopeptide crosslinks at a single point in time may potentially be used as indicators of current bone status, particularly at non-spine skeletal sites.

Aged↗