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Calcium and vitamin D supplements reduce tooth loss in the elderly
Calcium and Vitamin D Supplements Reduce Tooth Loss in the Elderly Elizabeth A. Krall, PhD, Carolyn Wehler, RDH, BS, Raul I. Garcia, DMD, Susan S. Harris, DSc, Bess Dawson-Hughes, MD 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. Am J Med. 2001;111: 452– 456. 䉷2001 by Excerpta Medica, Inc.
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vented by a diet containing an adequate amount of calcium or a high calcium to phosphorus ratio (15–17). Three studies in humans have examined associations between calcium supplementation and oral bone status (18 –20). However, these studies were short-term, used small sample sizes, and likely had inadequate power to evaluate the effect of supplements on the risk of tooth loss. Therefore, the benefits of increased intakes of calcium and vitamin D on tooth retention are unknown. Our study aim was to determine if the risk of tooth loss differed among elderly subjects who were randomly assigned supplements of calcium and vitamin D compared with subjects given a placebo, adjusting for factors that are related to tooth loss.
ooth loss has been associated with low bone mineral density in many (1– 4), but not all, cross-sectional studies (5–7). Longitudinal studies of bone mineral status in the mandible (8) or alveolar bone (9) have reported positive correlations of oral bone loss with bone loss at nonoral skeletal sites. In a 7-year prospective study, rates of bone loss from the hip and total body were more rapid in postmenopausal women who lost teeth than in women who retained teeth (10). These findings suggest that osteoporosis and osteopenia can influence oral bone and dentition status. Randomized, controlled trials have demonstrated that increased intake of calcium or vitamin D slows the rate of bone mineral loss at such sites as the hip and forearm, as well as the total body (11–14). Osteoporosis-like changes in the oral bone of animals have been shown to be preFrom the Department of Health Policy and Health Services Research, Boston University Goldman School of Dental Medicine (EAK, CW, RIG), Boston, Massachusetts; Calcium and Bone Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University (EAK, SSH, BDH), Boston, Massachusetts; and Veterans Affairs Dental Longitudinal Study, Veterans Affairs Boston Healthcare System (RIG), Boston, Massachusetts. Supported by Grant AG10353 from the National Institutes of Health and by an agreement (58-1950-001) with the U.S. Department of Agriculture. Dr. Garcia is supported by Grant K24 DE00419 from the National Institute of Dental and Craniofacial Research. He was a Career Development Awardee from the Health Services Research and Development Service, US Department of Veterans Affairs. Requests for reprints should be addressed to Elizabeth A. Krall, PhD, Department of Health Policy and Health Services Research, Boston University Goldman School of Dental Medicine, 715 Albany Street, Room B324, Boston, Massachusetts 02118. Manuscript submitted February 13, 2001, and accepted in revised form July 3, 2001. 452
䉷2001 by Excerpta Medica, Inc. All rights reserved.
SUBJECTS AND METHODS Information on tooth loss and oral health status was obtained from 145 subjects who completed a 3-year, double-blind, randomized, placebo-controlled trial of the effect of calcium and vitamin D supplementation on bone loss from the hip (11), as well as a 2-year follow-up study during which study supplements were discontinued (21). Collection of dental information was added to the protocol after the randomized trial began (see Figure for the time line of dental data collection in reference to the parent studies). At entry into the randomized trial, each subject was healthy and ambulatory; had bone mineral density of the femoral neck that was not lower than 2 standard deviations below an age- and sex-matched reference value; and was not taking bisphosphonates, calcitonin, estrogen, tes0002-9343/01/$–see front matter PII S0002-9343(01)00899-3
Calcium and Vitamin D Supplements Reduce Tooth Loss/Krall et al
Figure. Data collection timeline for oral variables. The shaded portion of the line indicates the 3-year, randomized, placebocontrolled trial of calcium and vitamin D supplements, and the unshaded portion indicates the 2-year follow-up period after discontinuation of study supplements.
tosterone, tamoxifen, or calcium and vitamin D supplements. Most (98%) subjects were white. Informed consent was obtained on forms approved by the Human Investigation Review Committee of Tufts University, Boston, Massachusetts.
Randomized Controlled Trial (Baseline to Year 3) Subjects in the supplemented group took elemental calcium as calcium citrate malate, 500 mg per day, and cholecalciferol, 700 IU per day. Subjects in the placebo group took the same number of pills, each containing microcrystalline cellulose. Mean compliance, based on pill counts every 6 months, was 93% in the supplemented group and 92% in the placebo group. Use of calcium and vitamin D supplements other than the study supplement was discouraged during the trial. Dietary intakes of calcium and vitamin D within the previous 6 months were measured every 6 months using a food frequency questionnaire (14), and average intake during the trial was computed from these repeated questionnaires. The number of teeth present, including third molars, was counted by the clinical trial’s nurse practitioner at the 18-month examination. Questionnaires administered at 18 months and 3 years asked the number of teeth lost in the 1-year interval between the 6- and 18-month examinations, and in the 1.5-year interval between the 18month and 3-year examinations. The number of teeth present at the 6-month examination and the number lost during the last 2.5 years of the trial were computed from the tooth counts and questionnaires.
Follow-up (Years 4 and 5) After the randomized trial, subjects voluntarily entered a 2-year observational study during which the study supplements were withdrawn, but subjects could elect to take any nutritional supplements. Use of all nutritional supplements containing calcium or vitamin D in the previous year was documented by questionnaires at the 4- and 5-year examinations. Dietary intakes of calcium and vitamin D within the previous 6 months were measured on an annual basis by the food frequency questionnaire. To-
tal calcium and vitamin D intakes (diet plus supplements) at the 4- and 5-year examinations were computed, and the average of these two intakes was used in analyses of tooth loss during follow-up. Total calcium intake during follow-up was dichotomized into categories of less than 1000 mg per day or 1000 mg or more per day. This cutoff value divided the group at approximately the median calcium intake (1030 mg/day). At the 5-year examination, subjects reported oral hygiene practices (frequency of tooth brushing and flossing, professional visits for teeth cleaning), history of treatment for gum disease, and number of teeth lost since the end of the randomized trial. Subjects were also invited to participate in a clinical oral examination performed by a calibrated dental examiner. The examiner recorded the presence or absence of clinically evident caries on each tooth, as well as periodontal disease status on up to 10 teeth (1 anterior, 2 left posterior, and 2 right posterior teeth in upper and lower jaws), using a modified Community Periodontal Index of Treatment Needs (22). A PDT Perio-Probe Type E (ProDentec; Batesville, Arizona) was used to determine probing pocket depth. The worst site per tooth was recorded. Scores of 3 or 4 indicate periodontal disease with pockets 3.5 mm or greater. The subjects for analysis (n ⫽ 145) were selected on the basis of having completed the randomized trial and the follow-up study, as well as having complete clinical oral examination data. A total of 295 subjects were followed over the 5-year period, but 150 were excluded from analysis (34 completely edentulous, 4 initiated hormone replacement therapy after baseline, 112 did not participate in the oral examination). Of the subjects who did not participate in the oral examination, 3 refused and 54 had a history of a medical contraindication for periodontal probing without antibiotic premedication, such as rheumatic fever, heart murmur, or prosthetic joint (23). There were no differences in age, sex, smoking status, or number of teeth lost between subjects with or without the oral examination. Subjects who participated in the oral examination had more teeth at 6 months than did nonparticipants (22 ⫾ 7 vs. 17 ⫾ 11, P ⬍0.01) and were more likely to have been in the supplemented than in the placebo group (56% vs. 43%, P ⫽ 0.02).
Statistical Analysis Independent-sample t tests, two-sample median tests, and the chi-squared test were used to compare characteristics between groups. All P values reported are two sided. The odds ratio (OR) of tooth loss and 95% confidence interval (CI) were estimated from stepwise multivariate logistic regression models (SAS version 8.0; SAS Institute, Cary, North Carolina), separately for the randomized trial (6 months through year 3) and follow-up phase (years 4 and 5). The dependent variable in each analysis was loss of any teeth (yes/no).
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Table 1. Characteristics of 145 Subjects Measured at 6-Month Examination of Randomized Controlled Trial, by Supplement Status Characteristic
Placebo (n ⫽ 63)
Calcium and Vitamin D (n ⫽ 82)
P Value
Number (%), Mean ⫾ SD, or Median (Interquartile Range) Age (years) Male sex Education ⬎high school Current smokers Ever diagnosed with diabetes Teeth remaining Teeth lost during trial Maximum number of teeth lost
72 ⫾ 5 26 (41) 40 (63) 4 (6) 2 (3) 22 ⫾ 7 0 (0-1) 3
For tooth loss during the randomized trial, independent variables in the initial model included supplement group (placebo or calcium and vitamin D), current smoker (yes/no), baseline age, education beyond high school (yes/no), presence of diabetes (yes/no), sex, and interactions between supplement status and smoking status and sex. Analysis of the odds of tooth loss during the follow-up period was performed as above with the same independent variables and interaction terms, with the exception that calcium intake level (less than 1000 mg/day or 1000 mg/day or greater) was substituted for the supplement group and prior calcium and vitamin D treatment status was included as an independent variable. In all models, a variable entered into the final model if its P value was less than 0.15 and remained if P was less than or equal to 0.05.
RESULTS Randomized Controlled Trial
The 62 men and 83 women were a mean (⫾ SD) of 71 ⫾ 5 years of age and had 22 ⫾ 7 teeth remaining at the 6-month examination (Table 1). During the randomized trial, 17 of the 63 subjects (27%) in the placebo group and 11 of the 82 subjects (13%) in the supplemented group lost one or more teeth. Results of the stepwise logistic regression analysis indicated that only supplement status was significantly associated with the odds of tooth loss during the randomized trial (OR ⫽ 0.4; 95% CI: 0.2 to 0.9; P ⬍ 0.05). None of the interaction terms was statistically significant, indicating that the effect of the supplements did not differ by sex or smoking status.
Follow-up During follow-up, 91 subjects (63%) reported use of calcium supplements and 78 subjects (54%) reported use of vitamin D supplements at any time. Their supplements 454
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71 ⫾ 4 36 (44) 55 (67) 6 (7) 6 (7) 22 ⫾ 7 0 (0-0) 6
0.45 0.75 0.65 0.82 0.27 0.94 0.04
contributed calcium, 545 ⫾ 456 mg, and vitamin D, 431 ⫾ 463 IU, daily. Average calcium intakes in the lower (705 ⫾ 261 mg/day) and higher (1166 ⫾ 294 mg/day) calcium intake categories during follow-up were similar to those in the placebo (711 ⫾ 185 mg/day) and supplemented (1492 ⫾ 378 mg/day) groups during the randomized trial. Subject characteristics at the beginning of follow-up are shown in Table 2. Forty subjects (59%) at the lower calcium intake level lost one or more teeth during followup, compared with 31 subjects (40%) at the higher calcium intake level. Only total calcium intake level was significantly associated with the odds of tooth loss during follow-up (OR ⫽ 0.5; 95% CI: 0.2 to 0.9; P ⫽ 0.03). Vitamin D intake was not independently related to tooth loss risk. We did not see an effect of prior calcium and vitamin D treatment on the risk of tooth loss during follow-up. There were no differences in oral hygiene practices (professional visits for cleaning, frequency of brushing and flossing), history of treatment for periodontal disease, or presence of caries or periodontal disease between the treatment groups (Table 3).
DISCUSSION Our results support a relation between calcium and vitamin D intake and the risk of tooth loss. During the randomized trial and follow-up period, average calcium and vitamin D levels in the higher intake groups approximated the dietary reference intake values for adults in the United States, which are 1000 to 1200 mg of calcium and 400 to 600 IU of vitamin D (24). Confirmation of our results would suggest that maintenance of the recommended calcium and vitamin D intakes will have a beneficial effect on tooth retention. However, this study has several limitations. Because tooth loss was not an original study outcome, tooth
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Calcium and Vitamin D Supplements Reduce Tooth Loss/Krall et al
Table 2. Characteristics of 145 Subjects Measured at the Beginning of the 2-Year follow-up Period, by Calcium Intake Level Calcium Characteristic
⬍1000 mg/day (n ⫽ 68)
ⱖ1000 mg/day (n ⫽ 77)
P Value
Number (%), Mean ⫾ SD, or Median (Interquartile Range) Age (years) Male sex Education ⬎high school Current smokers Ever diagnosed with diabetes Teeth remaining Teeth lost during follow-up Maximum number of teeth lost
74 ⫾ 5 36 (53) 43 (63) 3 (4) 5 (7) 21 ⫾ 8 0 (0-2) 7
counts, caries assessment, and periodontal examination were available only on a nonrandom subset of subjects who completed both studies. Furthermore, the assessment of the number of teeth lost between the 6- and 18month examinations was dependent on self-reports. A study of oral health status in older persons in New England, however, demonstrated that subjects can provide accurate self-reports of the number of teeth present (25). Because the comprehensive clinical dental assessment was performed only at the final examination, the caries and periodontal status of teeth that were lost during the previous 5 years were unknown. If the remaining teeth serve as valid indicators of a person’s long-term oral health, it is unlikely that the supplemented and placebo groups differed greatly at the beginning of the randomized trial. It was not possible also to separate the effects of calcium and vitamin D, because single nutrients were not tested in the trial and most subjects who voluntarily used nutritional supplements during follow-up used both nutrients. These shortcomings need to be corrected in future studies.
74 ⫾ 4 26 (34) 52 (67) 7 (9) 3 (4) 22 ⫾ 7 0 (0-1) 9
0.55 0.02 0.89 0.27 0.36 0.55 0.03
Previous studies of the effect of calcium intakes on oral health did not include tooth loss as an outcome measurement, but instead focused on surrogate outcomes such as oral bone loss and clinical indicators of periodontal disease. Nishida et al. (26) recently discussed an analysis of dietary intake surveys and periodontal data in over 12,000 adults from the third National Health and Nutrition Examination Survey. After adjusting for age and smoking status, there was an inverse association between calcium intake level (from diet only) and the odds of having periodontal disease (defined as mean periodontal attachment loss 1.5 mm or greater) among younger adults. The odds nearly doubled in both men and women whose calcium intake was below 800 mg per day relative to a higher intake. Although these findings support an association between low dietary calcium and increased risk of periodontal disease, the study was limited by its crosssectional design and lack of data on calcium supplement use. A few earlier, short-term studies in humans examined the effects of calcium supplements on alveolar bone loss
Table 3. Oral Health Variables Measured in 145 Subjects at the End of the Follow-up Period, by Supplement Status Characteristic
Placebo (n ⫽ 63)
Calcium and Vitamin D (n ⫽ 82)
P Value
Number (%) or Median (Interquartile Range) Teeth cleaned professionally in previous year Floss at least once per week Brush at least twice per day History of periodontal disease treatment Teeth needing caries treatment Teeth with periodontal pockets ⱖ3.5 mm
56 (89)
74 (90)
0.79
22 (35) 48 (76) 26 (41) 0 (0,0) 9 (0-19)
25 (31) 64 (78) 28 (34) 0 (0,4) 10 (3-20)
0.57 0.85 0.38 0.18 0.92
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in patients with periodontal disease with conflicting results (18 –20); animal experiments also showed that diets with inadequate calcium (15–17) produce changes in alveolar bone that resemble osteoporosis. It is not known if prevention of these changes will retard periodontal disease progression or tooth loss. Given the apparent episodic nature of periodontal infection and tissue destruction, follow-up periods of at least several years may be needed to detect a beneficial effect of nutrient intakes on oral bone and tooth retention. It would also appear that the increased intakes must be sustained to achieve a longterm benefit. We saw no residual effect of the calcium and vitamin D supplements that were taken during the trial on the risk of tooth loss during the follow-up period. Similar findings were reported with respect to bone turnover and rates of bone loss at the hip and total body (21). In summary, calcium and vitamin D supplements were associated with a lower risk of tooth loss in elderly men and women. These findings need to be confirmed in an intervention trial in which tooth and oral bone loss are primary aims and additional risk factors for tooth loss are measured throughout the trial. If nutritional supplementation is found to be effective, such inexpensive and accessible measures could have a major benefit on the public’s oral health.
REFERENCES 1. Mohammad AR, Bauer RL, Yeh CK. Spinal bone density and tooth loss in a cohort of postmenopausal women. Int J Prosthodont. 1997;10:381–385. 2. May H, Reader R, Murphy S, Khaw KT. Self-reported tooth loss and bone mineral density in older men and women. Age Ageing. 1995; 24:217–221. 3. Krall EA, Dawson-Hughes B, Papas A, Garcia RI. Tooth loss and skeletal bone density in healthy postmenopausal women. Osteoporos Int. 1994;4:104–109. 4. Daniell HW. Postmenopausal tooth loss. Contributions to edentulism by osteoporosis and cigarette smoking. Arch Intern Med. 1983;143:1678–1682. 5. Weyant RJ, Pearlstein ME, Churak AP, et al. The association between osteopenia and periodontal attachment loss in older women. J Periodontol. 1999;70:982–991. 6. Earnshaw SA, Keating N, Hosking DJ, et al. Tooth counts do not predict bone mineral density in early postmenopausal Caucasian women. EPIC study group. Int J Epidemiol. 1998;27:479– 483. 7. Elders PJ, Habets LL, Netelenbos JC, et al. The relation between periodontitis and systemic bone mass in women between 46 and 55 years of age. J Clin Periodontol. 1992;19:492– 496. 8. von Wowern N. Bone mineral content of mandibles: normal reference values—rate of age-related bone loss. Calcif Tissue Int. 1988; 43:193–198.
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9. Payne JB, Reinhardt RA, Nummikoski PV, Patil KD. Longitudinal alveolar bone loss in postmenopausal osteoporotic/osteopenic women. Osteoporos Int. 1999;10:34– 40. 10. Krall EA, Garcia R, Dawson-Hughes B. Increased risk of tooth loss is related to bone loss at the whole body, hip and spine. Calcif Tissue Int. 1996;59:433– 437. 11. Dawson-Hughes B, Harris SS, Krall EA, Dallal GE. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med. 1997;337:670– 676. 12. Chevally T, Rizzoli R, Nydegger V, et al. Effects of calcium supplements on femoral bone mineral density and vertebral fracture rate in vitamin D–replete elderly patients. Osteoporos Int. 1994;4: 245–252. 13. Prince R, Devine A, Dick I, et al. The effects of calcium supplementation (milk powder or tablets) and exercise on bone density in postmenopausal women. J Bone Miner Res. 1995;10:1068–1075. 14. Dawson-Hughes B, Dallal GE, Krall EA, et al. A controlled trial of the effect of calcium supplementation on bone density in postmenopausal women. N Engl J Med. 1990;323:878– 883. 15. Bissada NF, DeMarco TJ. The effect of a hypocalcemic diet on the periodontal structures of the adult rat. J Periodontol. 1974;45: 739–745. 16. Oliver WM. The effect of deficiencies of calcium, vitamin D or calcium and vitamin D and of variations in the source of dietary protein on the supporting tissues of the rat molar. J Periodontol Res. 1969;4:56– 69. 17. Ferguson HW, Hartles RL. The effects of diets deficient in calcium or phosphorus in the presence and absence of supplements of vitamin D on the secondary cementum and alveolar bone of young rats. Arch Oral Biol. 1964;9:647– 658. 18. Uhrbom E, Jacobson L. Calcium and periodontitis: clinical effect of calcium medication. J Clin Periodontol. 1984;11:230–241. 19. Krook L, Lutwak L, Whalen JP, et al. Human periodontal disease. Morphology and response to calcium therapy. Cornell Vet. 1972; 62:32–53. 20. Spiller WF. A clinical evaluation of calcium therapy for periodontal disease. Dent Dig. 1971;77:522–526. 21. Dawson-Hughes B, Harris SS, Krall EA, Dallal GE. Effect of withdrawal of calcium and vitamin D supplements on bone mass in elderly men and women. Am J Clin Nutr. 2000;72:745–750. 22. Ainamo J, Barmes D, Beagrie G, et al. Development of the World Health Organization (WHO) community periodontal index of treatment needs (CPITN). Int Dent J. 1982;32:281–291. 23. Tong DC, Rothwell BR. Antibiotic prophylaxis in dentistry: a review and practice recommendations. J Am Dent Assoc. 2000;131: 366–374. 24. Bloch AS, Shils ME. National and international recommended dietary reference values. In: Shils ME, Olson JA, Shike M, Ross AC, eds. Modern Nutrition in Health and Disease. Baltimore: Williams and Wilkins; 1999:A19–A48. 25. Douglass CW, Berlin J, Tennestedt S. The validity of self-reported oral health status in the elderly. J Public Health Dent. 1991;51: 220–222. 26. Nishida M, Grossi SG, Dunford RG, et al. Calcium and the risk for periodontal disease. J Periodontol. 2000;71:1057–1066.
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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. Am J Med. 2001;111: 452– 456. 䉷2001 by Excerpta Medica, Inc.
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vented by a diet containing an adequate amount of calcium or a high calcium to phosphorus ratio (15–17). Three studies in humans have examined associations between calcium supplementation and oral bone status (18 –20). However, these studies were short-term, used small sample sizes, and likely had inadequate power to evaluate the effect of supplements on the risk of tooth loss. Therefore, the benefits of increased intakes of calcium and vitamin D on tooth retention are unknown. Our study aim was to determine if the risk of tooth loss differed among elderly subjects who were randomly assigned supplements of calcium and vitamin D compared with subjects given a placebo, adjusting for factors that are related to tooth loss.
ooth loss has been associated with low bone mineral density in many (1– 4), but not all, cross-sectional studies (5–7). Longitudinal studies of bone mineral status in the mandible (8) or alveolar bone (9) have reported positive correlations of oral bone loss with bone loss at nonoral skeletal sites. In a 7-year prospective study, rates of bone loss from the hip and total body were more rapid in postmenopausal women who lost teeth than in women who retained teeth (10). These findings suggest that osteoporosis and osteopenia can influence oral bone and dentition status. Randomized, controlled trials have demonstrated that increased intake of calcium or vitamin D slows the rate of bone mineral loss at such sites as the hip and forearm, as well as the total body (11–14). Osteoporosis-like changes in the oral bone of animals have been shown to be preFrom the Department of Health Policy and Health Services Research, Boston University Goldman School of Dental Medicine (EAK, CW, RIG), Boston, Massachusetts; Calcium and Bone Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University (EAK, SSH, BDH), Boston, Massachusetts; and Veterans Affairs Dental Longitudinal Study, Veterans Affairs Boston Healthcare System (RIG), Boston, Massachusetts. Supported by Grant AG10353 from the National Institutes of Health and by an agreement (58-1950-001) with the U.S. Department of Agriculture. Dr. Garcia is supported by Grant K24 DE00419 from the National Institute of Dental and Craniofacial Research. He was a Career Development Awardee from the Health Services Research and Development Service, US Department of Veterans Affairs. Requests for reprints should be addressed to Elizabeth A. Krall, PhD, Department of Health Policy and Health Services Research, Boston University Goldman School of Dental Medicine, 715 Albany Street, Room B324, Boston, Massachusetts 02118. Manuscript submitted February 13, 2001, and accepted in revised form July 3, 2001. 452
䉷2001 by Excerpta Medica, Inc. All rights reserved.
SUBJECTS AND METHODS Information on tooth loss and oral health status was obtained from 145 subjects who completed a 3-year, double-blind, randomized, placebo-controlled trial of the effect of calcium and vitamin D supplementation on bone loss from the hip (11), as well as a 2-year follow-up study during which study supplements were discontinued (21). Collection of dental information was added to the protocol after the randomized trial began (see Figure for the time line of dental data collection in reference to the parent studies). At entry into the randomized trial, each subject was healthy and ambulatory; had bone mineral density of the femoral neck that was not lower than 2 standard deviations below an age- and sex-matched reference value; and was not taking bisphosphonates, calcitonin, estrogen, tes0002-9343/01/$–see front matter PII S0002-9343(01)00899-3
Calcium and Vitamin D Supplements Reduce Tooth Loss/Krall et al
Figure. Data collection timeline for oral variables. The shaded portion of the line indicates the 3-year, randomized, placebocontrolled trial of calcium and vitamin D supplements, and the unshaded portion indicates the 2-year follow-up period after discontinuation of study supplements.
tosterone, tamoxifen, or calcium and vitamin D supplements. Most (98%) subjects were white. Informed consent was obtained on forms approved by the Human Investigation Review Committee of Tufts University, Boston, Massachusetts.
Randomized Controlled Trial (Baseline to Year 3) Subjects in the supplemented group took elemental calcium as calcium citrate malate, 500 mg per day, and cholecalciferol, 700 IU per day. Subjects in the placebo group took the same number of pills, each containing microcrystalline cellulose. Mean compliance, based on pill counts every 6 months, was 93% in the supplemented group and 92% in the placebo group. Use of calcium and vitamin D supplements other than the study supplement was discouraged during the trial. Dietary intakes of calcium and vitamin D within the previous 6 months were measured every 6 months using a food frequency questionnaire (14), and average intake during the trial was computed from these repeated questionnaires. The number of teeth present, including third molars, was counted by the clinical trial’s nurse practitioner at the 18-month examination. Questionnaires administered at 18 months and 3 years asked the number of teeth lost in the 1-year interval between the 6- and 18-month examinations, and in the 1.5-year interval between the 18month and 3-year examinations. The number of teeth present at the 6-month examination and the number lost during the last 2.5 years of the trial were computed from the tooth counts and questionnaires.
Follow-up (Years 4 and 5) After the randomized trial, subjects voluntarily entered a 2-year observational study during which the study supplements were withdrawn, but subjects could elect to take any nutritional supplements. Use of all nutritional supplements containing calcium or vitamin D in the previous year was documented by questionnaires at the 4- and 5-year examinations. Dietary intakes of calcium and vitamin D within the previous 6 months were measured on an annual basis by the food frequency questionnaire. To-
tal calcium and vitamin D intakes (diet plus supplements) at the 4- and 5-year examinations were computed, and the average of these two intakes was used in analyses of tooth loss during follow-up. Total calcium intake during follow-up was dichotomized into categories of less than 1000 mg per day or 1000 mg or more per day. This cutoff value divided the group at approximately the median calcium intake (1030 mg/day). At the 5-year examination, subjects reported oral hygiene practices (frequency of tooth brushing and flossing, professional visits for teeth cleaning), history of treatment for gum disease, and number of teeth lost since the end of the randomized trial. Subjects were also invited to participate in a clinical oral examination performed by a calibrated dental examiner. The examiner recorded the presence or absence of clinically evident caries on each tooth, as well as periodontal disease status on up to 10 teeth (1 anterior, 2 left posterior, and 2 right posterior teeth in upper and lower jaws), using a modified Community Periodontal Index of Treatment Needs (22). A PDT Perio-Probe Type E (ProDentec; Batesville, Arizona) was used to determine probing pocket depth. The worst site per tooth was recorded. Scores of 3 or 4 indicate periodontal disease with pockets 3.5 mm or greater. The subjects for analysis (n ⫽ 145) were selected on the basis of having completed the randomized trial and the follow-up study, as well as having complete clinical oral examination data. A total of 295 subjects were followed over the 5-year period, but 150 were excluded from analysis (34 completely edentulous, 4 initiated hormone replacement therapy after baseline, 112 did not participate in the oral examination). Of the subjects who did not participate in the oral examination, 3 refused and 54 had a history of a medical contraindication for periodontal probing without antibiotic premedication, such as rheumatic fever, heart murmur, or prosthetic joint (23). There were no differences in age, sex, smoking status, or number of teeth lost between subjects with or without the oral examination. Subjects who participated in the oral examination had more teeth at 6 months than did nonparticipants (22 ⫾ 7 vs. 17 ⫾ 11, P ⬍0.01) and were more likely to have been in the supplemented than in the placebo group (56% vs. 43%, P ⫽ 0.02).
Statistical Analysis Independent-sample t tests, two-sample median tests, and the chi-squared test were used to compare characteristics between groups. All P values reported are two sided. The odds ratio (OR) of tooth loss and 95% confidence interval (CI) were estimated from stepwise multivariate logistic regression models (SAS version 8.0; SAS Institute, Cary, North Carolina), separately for the randomized trial (6 months through year 3) and follow-up phase (years 4 and 5). The dependent variable in each analysis was loss of any teeth (yes/no).
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Table 1. Characteristics of 145 Subjects Measured at 6-Month Examination of Randomized Controlled Trial, by Supplement Status Characteristic
Placebo (n ⫽ 63)
Calcium and Vitamin D (n ⫽ 82)
P Value
Number (%), Mean ⫾ SD, or Median (Interquartile Range) Age (years) Male sex Education ⬎high school Current smokers Ever diagnosed with diabetes Teeth remaining Teeth lost during trial Maximum number of teeth lost
72 ⫾ 5 26 (41) 40 (63) 4 (6) 2 (3) 22 ⫾ 7 0 (0-1) 3
For tooth loss during the randomized trial, independent variables in the initial model included supplement group (placebo or calcium and vitamin D), current smoker (yes/no), baseline age, education beyond high school (yes/no), presence of diabetes (yes/no), sex, and interactions between supplement status and smoking status and sex. Analysis of the odds of tooth loss during the follow-up period was performed as above with the same independent variables and interaction terms, with the exception that calcium intake level (less than 1000 mg/day or 1000 mg/day or greater) was substituted for the supplement group and prior calcium and vitamin D treatment status was included as an independent variable. In all models, a variable entered into the final model if its P value was less than 0.15 and remained if P was less than or equal to 0.05.
RESULTS Randomized Controlled Trial
The 62 men and 83 women were a mean (⫾ SD) of 71 ⫾ 5 years of age and had 22 ⫾ 7 teeth remaining at the 6-month examination (Table 1). During the randomized trial, 17 of the 63 subjects (27%) in the placebo group and 11 of the 82 subjects (13%) in the supplemented group lost one or more teeth. Results of the stepwise logistic regression analysis indicated that only supplement status was significantly associated with the odds of tooth loss during the randomized trial (OR ⫽ 0.4; 95% CI: 0.2 to 0.9; P ⬍ 0.05). None of the interaction terms was statistically significant, indicating that the effect of the supplements did not differ by sex or smoking status.
Follow-up During follow-up, 91 subjects (63%) reported use of calcium supplements and 78 subjects (54%) reported use of vitamin D supplements at any time. Their supplements 454
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71 ⫾ 4 36 (44) 55 (67) 6 (7) 6 (7) 22 ⫾ 7 0 (0-0) 6
0.45 0.75 0.65 0.82 0.27 0.94 0.04
contributed calcium, 545 ⫾ 456 mg, and vitamin D, 431 ⫾ 463 IU, daily. Average calcium intakes in the lower (705 ⫾ 261 mg/day) and higher (1166 ⫾ 294 mg/day) calcium intake categories during follow-up were similar to those in the placebo (711 ⫾ 185 mg/day) and supplemented (1492 ⫾ 378 mg/day) groups during the randomized trial. Subject characteristics at the beginning of follow-up are shown in Table 2. Forty subjects (59%) at the lower calcium intake level lost one or more teeth during followup, compared with 31 subjects (40%) at the higher calcium intake level. Only total calcium intake level was significantly associated with the odds of tooth loss during follow-up (OR ⫽ 0.5; 95% CI: 0.2 to 0.9; P ⫽ 0.03). Vitamin D intake was not independently related to tooth loss risk. We did not see an effect of prior calcium and vitamin D treatment on the risk of tooth loss during follow-up. There were no differences in oral hygiene practices (professional visits for cleaning, frequency of brushing and flossing), history of treatment for periodontal disease, or presence of caries or periodontal disease between the treatment groups (Table 3).
DISCUSSION Our results support a relation between calcium and vitamin D intake and the risk of tooth loss. During the randomized trial and follow-up period, average calcium and vitamin D levels in the higher intake groups approximated the dietary reference intake values for adults in the United States, which are 1000 to 1200 mg of calcium and 400 to 600 IU of vitamin D (24). Confirmation of our results would suggest that maintenance of the recommended calcium and vitamin D intakes will have a beneficial effect on tooth retention. However, this study has several limitations. Because tooth loss was not an original study outcome, tooth
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Table 2. Characteristics of 145 Subjects Measured at the Beginning of the 2-Year follow-up Period, by Calcium Intake Level Calcium Characteristic
⬍1000 mg/day (n ⫽ 68)
ⱖ1000 mg/day (n ⫽ 77)
P Value
Number (%), Mean ⫾ SD, or Median (Interquartile Range) Age (years) Male sex Education ⬎high school Current smokers Ever diagnosed with diabetes Teeth remaining Teeth lost during follow-up Maximum number of teeth lost
74 ⫾ 5 36 (53) 43 (63) 3 (4) 5 (7) 21 ⫾ 8 0 (0-2) 7
counts, caries assessment, and periodontal examination were available only on a nonrandom subset of subjects who completed both studies. Furthermore, the assessment of the number of teeth lost between the 6- and 18month examinations was dependent on self-reports. A study of oral health status in older persons in New England, however, demonstrated that subjects can provide accurate self-reports of the number of teeth present (25). Because the comprehensive clinical dental assessment was performed only at the final examination, the caries and periodontal status of teeth that were lost during the previous 5 years were unknown. If the remaining teeth serve as valid indicators of a person’s long-term oral health, it is unlikely that the supplemented and placebo groups differed greatly at the beginning of the randomized trial. It was not possible also to separate the effects of calcium and vitamin D, because single nutrients were not tested in the trial and most subjects who voluntarily used nutritional supplements during follow-up used both nutrients. These shortcomings need to be corrected in future studies.
74 ⫾ 4 26 (34) 52 (67) 7 (9) 3 (4) 22 ⫾ 7 0 (0-1) 9
0.55 0.02 0.89 0.27 0.36 0.55 0.03
Previous studies of the effect of calcium intakes on oral health did not include tooth loss as an outcome measurement, but instead focused on surrogate outcomes such as oral bone loss and clinical indicators of periodontal disease. Nishida et al. (26) recently discussed an analysis of dietary intake surveys and periodontal data in over 12,000 adults from the third National Health and Nutrition Examination Survey. After adjusting for age and smoking status, there was an inverse association between calcium intake level (from diet only) and the odds of having periodontal disease (defined as mean periodontal attachment loss 1.5 mm or greater) among younger adults. The odds nearly doubled in both men and women whose calcium intake was below 800 mg per day relative to a higher intake. Although these findings support an association between low dietary calcium and increased risk of periodontal disease, the study was limited by its crosssectional design and lack of data on calcium supplement use. A few earlier, short-term studies in humans examined the effects of calcium supplements on alveolar bone loss
Table 3. Oral Health Variables Measured in 145 Subjects at the End of the Follow-up Period, by Supplement Status Characteristic
Placebo (n ⫽ 63)
Calcium and Vitamin D (n ⫽ 82)
P Value
Number (%) or Median (Interquartile Range) Teeth cleaned professionally in previous year Floss at least once per week Brush at least twice per day History of periodontal disease treatment Teeth needing caries treatment Teeth with periodontal pockets ⱖ3.5 mm
56 (89)
74 (90)
0.79
22 (35) 48 (76) 26 (41) 0 (0,0) 9 (0-19)
25 (31) 64 (78) 28 (34) 0 (0,4) 10 (3-20)
0.57 0.85 0.38 0.18 0.92
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in patients with periodontal disease with conflicting results (18 –20); animal experiments also showed that diets with inadequate calcium (15–17) produce changes in alveolar bone that resemble osteoporosis. It is not known if prevention of these changes will retard periodontal disease progression or tooth loss. Given the apparent episodic nature of periodontal infection and tissue destruction, follow-up periods of at least several years may be needed to detect a beneficial effect of nutrient intakes on oral bone and tooth retention. It would also appear that the increased intakes must be sustained to achieve a longterm benefit. We saw no residual effect of the calcium and vitamin D supplements that were taken during the trial on the risk of tooth loss during the follow-up period. Similar findings were reported with respect to bone turnover and rates of bone loss at the hip and total body (21). In summary, calcium and vitamin D supplements were associated with a lower risk of tooth loss in elderly men and women. These findings need to be confirmed in an intervention trial in which tooth and oral bone loss are primary aims and additional risk factors for tooth loss are measured throughout the trial. If nutritional supplementation is found to be effective, such inexpensive and accessible measures could have a major benefit on the public’s oral health.
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9. Payne JB, Reinhardt RA, Nummikoski PV, Patil KD. Longitudinal alveolar bone loss in postmenopausal osteoporotic/osteopenic women. Osteoporos Int. 1999;10:34– 40. 10. Krall EA, Garcia R, Dawson-Hughes B. Increased risk of tooth loss is related to bone loss at the whole body, hip and spine. Calcif Tissue Int. 1996;59:433– 437. 11. Dawson-Hughes B, Harris SS, Krall EA, Dallal GE. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med. 1997;337:670– 676. 12. Chevally T, Rizzoli R, Nydegger V, et al. Effects of calcium supplements on femoral bone mineral density and vertebral fracture rate in vitamin D–replete elderly patients. Osteoporos Int. 1994;4: 245–252. 13. Prince R, Devine A, Dick I, et al. The effects of calcium supplementation (milk powder or tablets) and exercise on bone density in postmenopausal women. J Bone Miner Res. 1995;10:1068–1075. 14. Dawson-Hughes B, Dallal GE, Krall EA, et al. A controlled trial of the effect of calcium supplementation on bone density in postmenopausal women. N Engl J Med. 1990;323:878– 883. 15. Bissada NF, DeMarco TJ. The effect of a hypocalcemic diet on the periodontal structures of the adult rat. J Periodontol. 1974;45: 739–745. 16. Oliver WM. The effect of deficiencies of calcium, vitamin D or calcium and vitamin D and of variations in the source of dietary protein on the supporting tissues of the rat molar. J Periodontol Res. 1969;4:56– 69. 17. Ferguson HW, Hartles RL. The effects of diets deficient in calcium or phosphorus in the presence and absence of supplements of vitamin D on the secondary cementum and alveolar bone of young rats. Arch Oral Biol. 1964;9:647– 658. 18. Uhrbom E, Jacobson L. Calcium and periodontitis: clinical effect of calcium medication. J Clin Periodontol. 1984;11:230–241. 19. Krook L, Lutwak L, Whalen JP, et al. Human periodontal disease. Morphology and response to calcium therapy. Cornell Vet. 1972; 62:32–53. 20. Spiller WF. A clinical evaluation of calcium therapy for periodontal disease. Dent Dig. 1971;77:522–526. 21. Dawson-Hughes B, Harris SS, Krall EA, Dallal GE. Effect of withdrawal of calcium and vitamin D supplements on bone mass in elderly men and women. Am J Clin Nutr. 2000;72:745–750. 22. Ainamo J, Barmes D, Beagrie G, et al. Development of the World Health Organization (WHO) community periodontal index of treatment needs (CPITN). Int Dent J. 1982;32:281–291. 23. Tong DC, Rothwell BR. Antibiotic prophylaxis in dentistry: a review and practice recommendations. J Am Dent Assoc. 2000;131: 366–374. 24. Bloch AS, Shils ME. National and international recommended dietary reference values. In: Shils ME, Olson JA, Shike M, Ross AC, eds. Modern Nutrition in Health and Disease. Baltimore: Williams and Wilkins; 1999:A19–A48. 25. Douglass CW, Berlin J, Tennestedt S. The validity of self-reported oral health status in the elderly. J Public Health Dent. 1991;51: 220–222. 26. Nishida M, Grossi SG, Dunford RG, et al. Calcium and the risk for periodontal disease. J Periodontol. 2000;71:1057–1066.
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