Abstract
Objectives
Determine the level of calcium and vitamin D oral supplementation in patients in periodontal disease maintenance programs.
Design
Convenience survey.
Setting
St. Louis Metropolitan region.
Subjects and Methods
Patients (n=228) in two university-based, periodontal-disease maintenance programs.
Main Outcome Measures
Reported amounts of oral calcium and vitamin D supplementation were tested for differences based on gender and race.
Results
The last published recommended daily intakes from the United States (U.S.) Food and Nutrition Board (FNB) for adults >50 years of age are 1200 mg calcium and 400 IU vitamin D (or 600 IU if over 70). The mean age of the 228 patients (125 females and 103 males) was 63.6±11.0 years (standard deviation). Of the 228 patients surveyed: (1) 204(89%) were >50 years of age, and of these, only 15(7%) met the U.S. FNB’s recommended intakes of calcium and vitamin D from supplementation, (2) 138(66%) reported that they took no oral supplementation, with significantly more males (n=82) than females (n=56) not taking supplementation (p=0.03), (3) 88(39%) took calcium supplementation, with females (947±511mg/day) taking significantly (p<0.001) more than males (632±907mg/day), and (4) 66(29%) took vitamin D supplementation, with females(420±227 IU/day) taking approximately the same amount as males (443±317 IU/day, p>0.05). The amounts of oral supplementation did not vary with race (p>0.05).
Conclusion
The use of calcium and vitamin D supplementation has been promoted for years; yet the numbers of adults taking supplements remains low and the level of supplementation varies greatly. Knowledge of the benefits of supplementation needs to be better disseminated and research needs to be conducted to determine optimal levels of calcium and vitamin D supplementation.
Keywords: Calcium/therapeutic use, diet, nutrition, periodontal diseases/prevention and control, vitamin D
INTRODUCTION
Oral bone mass increases throughout infancy, childhood, and adolescence to reach a genetically determined peak bone mass in early adulthood. Thereafter, the oral bone, just as total skeletal bone, loses bone mass. The rate of increase and loss is dependent upon heredity and the availability of calcium and vitamin D. If calcium intakes are inadequate, skeletal calcium is resorbed to maintain the body’s calcium homeostasis, which is essential for life-sustaining processes–such as blood clotting, muscle contraction, and nerve excitability. The resorption of the body’s calcium is mediated by parathyroid hormone (PTH), which increases osteoclastic activity in bone to release stored calcium to the circulation and increases the synthesis of 1,25-dihydroxyvitamin D [1,25(OH)2D] (the biologically active form of vitamin D), which in turn increases the absorption of calcium from the intestine. The best way to estimate vitamin D intakes is to measure the serum levels of 25-hydroxyvitamin D [25(OH)D].1 When serum levels of 25(OH)D are low, there is decreased calcium absorption, increased PTH secretion, and increased osteoclastic activity.
In a September 2002 review of 180 articles on bone status and calcium intake, it was reported that 68 of 70 (97%) randomized clinical trials found that individuals who received calcium supplementation had greater gains in bone during growth, less loss of bone with age, and/or reduced fracture risk, relative to unsupplemented individuals, and that 85 of 110 (77%) observational studies found positive effects for calcium supplementation.2 It is also well established that vitamin D is essential for bone growth and that it has its greatest effect when combined with calcium supplementation.3-5 Dietary Reference Intakes [the last published recommendations of the U.S. Institute of Medicine’s Food and Nutrition Board (FNB)] suggests a total intake from diet and oral supplementation of 1200 mg/day calcium and 400 IU (10.0 μg)/day vitamin D for ages 51-70 and for those >70 years of age, 1200 mg calcium/day and 600 IU vitamin D (15.0 μg)/day.6 In the U.S., the median calcium intake for men 50 to 70 years of age is 708 mg/day and for women 571 mg/day and 702 and 517 mg/day respectively for those >70 years of age.7 Therefore, on average, adult men and women need to consume an additional 500-600 mg/day of calcium through food or supplementation, just to meet health needs.
There is also growing concern that recent studies have identified high prevalence’s of vitamin D insufficiency in otherwise healthy adults and that current FNB recommendations of vitamin D intake are inadequate. A number of investigators convincingly argue that serum 25(OH)D levels < 70-80 nmol/liter are deficient.8 Another source for information, the National Osteoporosis Foundation (NOF) recommends 1,000 mg calcium and 400-800 IU Vitamin D daily for adults <50 years of age, and for those >50 years of age, 1,200 mg calcium and 800-1,000 IU Vitamin D daily.9 A periodontal-disease, vitamin-D study of the Third National Health and Nutrition Examination Survey (NHANES III) data found that the majority of subjects had serum 25(OH)D levels far below 80 nmol/liter.10 As pointed out in recent studies, the older recommendations of 400 or 600 IU vitamin D/day were intended to maintain health and are inadequate for correcting vitamin D insufficiencies.11
It is reasonable to think that calcium and vitamin D affect oral bone in the same way that they affect other bones of the body, and various studies, including analyses of data from NHANES III, have found associations between periodontal health and intakes of calcium and vitamin D.10, 12Researchers have found that (1)optimal intakes of calcium and vitamin D slow bone resorption and speed bone formation, thereby reducing bone loss13, (2)vitamin D stimulates the expression of antimicrobial peptides (α- and β-defensins and cathelicidins),14, 15 and (3)vitamin D has an immunosuppressive effect on periodontal disease.10 As the levels of calcium and vitamin D oral supplementation for patients with periodontal disease are unknown, the purpose of this study was to survey adult patients in two university-based, periodontal-disease maintenance programs to determine their levels of calcium and vitamin D oral supplementation.
METHODS
Study Population
We conducted our survey at Southern Illinois University School of Dental Medicine (SIU-SDM) in Alton, Illinois and the Saint Louis University Center for Advanced Dental Education (SLU-CADE) in St. Louis, Missouri. Study subjects were recruited from periodontal-disease recall programs based at these two institutions, whose patient populations are from the Greater St. Louis region, an area comprising 12 counties in Eastern Missouri and Southern Illinois. According to the latest U.S. census, this area has a population of approximately 2.3 million, which makes it the 18th largest market area in the United States. There are approximately 920 patients in the periodontal-disease maintenance program at Southern Illinois University and 200 at Saint Louis University.
Patient Questionnaire
We obtained Institutional Review Board (IRB) approvals for our protocol and our use of a brief patient questionnaire at SIU-SDM, SLU-CADE, and Washington University in St. Louis (principal investigator’s home institution). Signs were posted in the periodontal maintenance program dental operatories at SIU-SDM and SLU-CADE, with the sign’s informing patients of a potential research study involving calcium and vitamin D. Interested patients were invited to complete our brief questionnaire, which requested information on age, gender, number of years postmenopausal, use of vitamin D and/or calcium supplements (including multivitamins and antacids), and use of bone-active prescription drugs (such as, risedronate,* alendronate,† raloxifene,‡ or estrogen).
Questionnaires were checked for completeness, and if additional information on amounts of calcium and vitamin D was needed after the patients had gone home, they were contacted by telephone.
Data Analysis
Data are reported as means ± standard deviation. For categorical variables, frequencies were calculated for patients who were or were not taking calcium/vitamin D and/or bone-active prescription drugs. Distributions of age, mg of calcium taken per day, and international units (IUs—40 IUs = 1 μg) of vitamin D taken per day were tested for normality with the Shapiro-Wilk W test, and equality of variances were tested with O’Brien, Brown-Forsythe, Levene, and Bartlett tests. Differences in responses based on gender, menopausal status, and race were tested for statistical significance with the chi-square test, Fisher’s exact test, analysis of variance (ANOVA) and Student’s t test. If data were non-normally distributed and/or variances were not equal, the Welch ANOVA and/or Wilcoxon tests were used. For those who took neither calcium nor vitamin D oral supplementation, the binomial test was used to determine if there were more males than females. This test is used when there are only two possible outcomes, with fixed rates of occurrence-in this case 0.5 for males and 0.5 for females.16 The chi-square, goodness-of-fit test was used to test for differences in racial proportions between respondents and the St. Louis region. If for the chi-square test, 20% of the cells had expected counts of less than 5, exact p values were calculated by means of data permutation. If default time limits were exceeded for calculations of exact p values, Monte Carlo estimates were used. Monte Carlo estimates and exact calculations of p values were performed with StatXact Statistical Software for Exact Nonparametric Inference (Version 6 with Cytel Studio™, Cytel Software Corporation, Cambridge, MA). All other statistical testing was performed with JMP Statistical Software (SAS Institute, Inc., Cary, NC).
RESULTS
From May 2003 through September 2004, 228 questionnaires were completed and returned. The racial make-up of the pooled sample was not significantly different (p = 0.15) from that for the St. Louis region. The mean age of the 228 patients surveyed was 63.6 ± 11.0 years, with 204 (89%) being over the age of 50 years. Males were significantly older (64.2 ± 9.5 years) than females (58.8 ± 11.9 years, Table 1). Postmenopausal women were significantly older than pre-menopausal women (p < 0.0001), and African Americans were significantly younger than Whites (p < 0.05). Eighty-eight patients reported taking oral calcium supplementation. Females took significantly more calcium than did men (p<0.001). The percentage of African Americans, who we surveyed, who took calcium (13.6%, n = 12, Table 1) was higher than the percentage of African Americans living in the St. Louis region (9.6%). Conversely, the percentage of Whites, who we surveyed, who took calcium (84.1%, n = 74, Table 1) was lower than the percentage of Whites living in the St. Louis region (87.9%).
Table 1.
Frequency and amounts of oral calcium and vitamin D supplementation used by the study population.
No calcium nor vitamin D supplements n = 138 |
Calcium supplements n = 88 |
Vitamin D supplements n = 66 |
||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Age |
Rx Drug§§ |
Age |
Calcium |
Rx Drug |
Age |
Vitamin D |
Rx Drug |
|||||||||
n | mean±SD | n | % | n | mean±SD | n | mg/day | n | % | n | mean±SD | n | IU/day | n | % | |
Gender |
||||||||||||||||
Male | 82 | 64.2±9.5* | 3 | 17 | 19 | 68.3±13.2 | 19 | 632±907 | 0 | 0 | 17 | 63.9±12.1 | 17 | 443±317 | 0 | 0 |
Female | 56 | 58.8±11.9 | 15 | 83† | 69 | 65.6±10.1 | 69 | 947±511‡ | 15 | 100§ | 49 | 65.9±10.7 | 49 | 420±227 | 11 | 100 |
Female | ||||||||||||||||
Menopausal Status |
||||||||||||||||
Pre | 9 | 43.4±7.3 | 0 | 0 | 3 | 40.3±12.3 | 3 | 687±458 | 1 | 7 | 3 | 40.3±12.3 | 3 | 400±200 | 1 | 9 |
Post | 46 | 62.1±10** | 15 | 100 | 66 | 66.7±8.4** | 66 | 959±513 | 14 | 93 | 46 | 67.6±8.3** | 46 | 421±231 | 10 | 91 |
Race |
||||||||||||||||
White African |
117 | 64.0±9.8†† | 17 | 94 | 74 | 68.2±9.2†† | 74 | 884±658 | 13 | 87 | 59 | 67.1±9.1†† | 59 | 430±260 | 10 | 91 |
American Indian |
15 | 50.2±9.1 | 1 | 6 | 12 | 53.9±13 | 12 | 819±422 | 2 | 13 | 7 | 51.3±16.2 | 7 | 393±164 | 1 | 9 |
Alaska | 1 | 44 | 0 | 0 | 1 | 67 | 1 | 600 | 0 | 0 | ||||||
Asian | 4 | 56.3±16.2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||||||
Hispanic | 0 | 0 | 1 | 60 | 1 | 1500 | 0 | 0 |
Male versus female,
p < 0.01;
p < 0.01;
p < 0.001;
p < 0.05
Pre versus post, p < 0.0001
White versus African American, p < 0.05
Bone-active prescription drugs
Sixty-six patients reported taking oral vitamin D supplementation. Unlike what was observed with calcium, there was no significant difference between men and women in the amounts of vitamin D supplementation taken. There was also no variation in vitamin D oral supplementation by race when compared to the makeup of the St. Louis region (p>0.05) (Table 1).
Among all subjects studied, 64 of the 228 (28%) took both oral calcium and vitamin D supplementation, and 138 of the 228 (61%) took no oral supplementation. Insufficient calcium and vitamin D intake, as assessed by supplementation amounts, was seen in 93% of the study population (Table 2).
Table 2.
Use of combined calcium and/or vitamin D supplementation in patients with periodontal disease.
Age |
Ca |
Vitamin D |
Rx Drug |
Meets FNB intakes§ |
Meets NOF intakes** |
|||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
n | mean±StD | n | mg/day | n | IU/day | n | % | n | % | n | % | |
Gender | ||||||||||||
Male | 15 | 64.9 ± 12.5 | 15 | 670 ± 1010 | 15 | 448 ± 338 | 0 | 0 | 2 | 13 | 1 | 17 |
Female | 49 | 65.9 ± 10.7 | 49 | 934 ± 548‡ | 49 | 420 ± 227 | 11 | 100 | 13 | 87 | 5 | 83 |
Female Menopausal | ||||||||||||
Status | ||||||||||||
Pre | 3 | 40.3 ± 12.3 | 3 | 687 ± 458 | 3 | 400 ± 200 | 1 | 9 | 13 | 100 | 0 | 0 |
Post | 46 | 67.6 ± 8.3* | 46 | 950 ± 554 | 46 | 421 ± 231 | 10 | 91 | 0 | 0.0 | 5 | 100 |
Race | ||||||||||||
White | 57 | 67.5 ± 9.0† | 57 | 886 ± 707 | 57 | 431 ± 265 | 10 | 91 | 14 | 93 | 6 | 100 |
African American | 7 | 51.3 ± 16.2 | 7 | 761 ± 487 | 7 | 393 ± 164 | 1 | 9 | 1 | 6 | 0 | 0 |
Indian/Alaska | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0 |
Asian | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0 |
Hispanic | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0 |
Pre versus post, p < 0.0001;
African American versus White, p < 0.05;
Male versus female, p < 0.01
Last published recommendations of the U. S. Food and Nutrition Board (FNB) of the Institute of Medicine
National Osteoporosis Foundation Recommendations
Thirty-three patients reported use of bone-active prescription drugs used for osteoporosis, specifically, risedronate (n = 5), alendronate (n = 13), estrogen (n = 4), raloxifene (n = 10), 1 unknown drug (unable to follow up with patient). Ninety-one percent of these patients were females, 97% were postmenopausal; and 91% were White (Table 1). Fifteen (45%) of these 33 patients indicated use of calcium supplements (1252 ± 456 mg/day); and 11 (33%) of the 33 indicated use of vitamin D supplements (473 ± 185 IU/day).
DISCUSSION
With regard to periodontal disease, the many benefits of calcium and/or vitamin D include strengthening the bone13, stimulating an antimicrobial effect,14, 15 and providing an immunosuppressive effect.10
The self-reported calcium and vitamin D intake levels would be insufficient by themselves to prevent deficiencies in our older adult population. Periodontal maintenance patients receive no advice concerning calcium and vitamin D intake at either institution. Accurate estimates of total intakes of calcium and vitamin D for our study subjects would have required performing dietary analyses, assessing sunlight exposures, or (in the case for vitamin D) assessing serum levels of 25(OH)D-none of which were done for our study. Nevertheless, of the patients we surveyed, 204 (89%) of 228 were over the age of 50, and based on the recommendations given in U. S. Dietary Reference Intakes,6 of these, only 15 (7%) obtained adequate intakes of calcium and vitamin D from oral supplementation, and only 6 (.03%) met the higher recommendations of the National Osteoporosis Foundation.9 Other studies of St. Louis women also indicate inadequate intakes (food and oral supplementation) of calcium and vitamin D.17, 18
The median calcium intakes (food plus oral supplementation) in the U.S. for men 50 to 70 years of age is 708 mg/day and for women 571 mg/day. Over the age of 70, the respective median intakes are 702 and 517 mg/day.7 U. S. Dietary Reference Intakes contains no table for vitamin D intakes such as it does for calcium; however, there is growing concern among researchers that recent studies have identified an alarming prevalence of vitamin D insufficiency in otherwise healthy adults and a re-emergence of vitamin D-deficiency-induced rickets.19 Many researchers now believe that for adults, daily supplementation with vitamin D at levels of, at least, 800 to1,000 IU (20 and 25 μg)/day would be safe and beneficial to health, and that the U. S. Food and Nutrition Board (FNB) of the Institute of Medicine needs to raise the recommended levels of intake for vitamin D.8
Dental Studies of the Effects of Calcium and/vitamin D on Alveolar Bone, Periodontal Health, and Tooth Retention
It has been found that increased periodontal attachment loss is related to decreased intakes of both calcium and vitamin D.10, 12 The investigators suggested that inadequate calcium intake increased risk of periodontal disease and could be related to decreased alveolar bone density. Inadequate intake of vitamin D could increase levels of periodontal disease either through an effect on bone mineral density or a suppression of vitamin D’s immunomodulatory effects.12 The anti-inflammatory effects of vitamin D (particularly the suppression of cytokine production) and vitamin D’s inducing the production of antimicrobial cathelicidin have been noted by various investigators.15, 20-24 There have been a number of studies that indicate that calcium/vitamin D intakes affect alveolar bone, periodontal health, and tooth retention, and even though there were limitations associated with these studies, there is strong evidence that calcium and vitamin D intake are positively associated with periodontal/alveolar bone health.25
Anti-resorptive agents
Fourteen percent (33/228) of the patients took bone-active prescription drugs, with the majority being female. Some patients in our study took risedronate or alendronate, which are bisphosphonates, which may improve periodontal health but also may cause osteonecrosis and painful refractory bone exposures of the jaws.26-31 The incidence of osteonecrosis of the jaw in patients taking oral bisphosphonate therapy for osteoporosis is low, with a reported risk of less than 1 in 100,000 patients.32 Some of the patients in our study took estrogen, which may benefit periodontal health.33-36 Other patients in our study took raloxifene [a selective estrogen receptor modulator, SERM]. No study has been published on the effect of this anti-resorptive agent on periodontal health.
Study limitations
The results of our study were drawn from self-reported questionnaires. Although the data were unconfirmed (except by telephone in a few cases), we gained knowledge about the use of oral calcium and vitamin D supplementation in a group of adults with known periodontal disease.
Conclusion
Calcium and vitamin D supplements are reasonably priced and widely available; yet many older adults in the U. S. take neither calcium nor vitamin D supplementation, and of those who do, intake levels are often inadequate.
Randomized clinical trials and observational studies have consistently demonstrated positive effects of calcium and/or vitamin D oral supplementation on postcranial (below the head) and alveolar bone.25 There are few health concerns associated with calcium and vitamin D use, but perhaps more important, there is considerable potential for health benefits,37 including periodontal health. Dentists and dental health professionals should advise all of their adult patients to follow the National Osteoporosis Foundation’s daily intake recommendations of 1,000 mg calcium and 400-800 IU vitamin D for adults <50 years of age, and 1200 mg calcium and 800-1,000 IU vitamin D for adults >50 years of age. Controlled studies should be conducted to establish the extent to which adequate intakes of calcium and vitamin D can stabilize/improve periodontal health.
Acknowledgments
This publication was made possible by Grant Number R21 DE016918-01A2 from the National Institute of Dental and Craniofacial Research (NIDCR) and Grant Number UL1 RR024992 from the National Center for Research Resources (NCRR), components of the U. S. National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NIDCR, NCRR, or NIH.
Footnotes
Actonel, Procter & Gamble Pharmaceuticals, Inc.
Fosamax, Merck Co., West Point, VA
Evista [raloxifene hydrochloride, a selective estrogen receptor modulator (SERM), Eli Lilly and Company, Indianapolis, IN)
Contributor Information
CHARLES F. HILDEBOLT, Washington University School of Medicine 510 South Kingshighway, St. Louis, MO, USA 63110 hildeboltc@mir.wustl.edu.
D. DOUGLAS MILEY, Southern Illinois University School of Dental Medicine 2800 College Avenue, Alton, Illinois, USA 62002; Saint Louis University Center for Advanced Dental Education 3320 Rutger St., St. Louis, MO, USA 63104 mileydd@slu.edu.
M. NATHALIA GARCIA, Southern Illinois University School of Dental Medicine 2800 College Avenue, Alton, Illinois, USA 62002; Saint Louis University Center for Advanced Dental Education 3320 Rutger St., St. Louis, MO, USA 63104 garciamn@slu.edu.
THOMAS K. PILGRAM, Washington University School of Medicine 510 South Kingshighway, St. Louis, MO, USA 63110 pilgramt@wustl.edu.
REX COUTURE, Washington University School of Medicine 510 South Kingshighway, St. Louis, MO, USA 63110 couturer@mir.wustl.edu.
CATHERINE ANDERSON SPEARIE, General Clinical Research Washington University School of Medicine 510 South Kingshighway, St. Louis, MO, USA 63110 anderson_c@gcrc.wustl.edu.
ROBERTO CIVITELLI, Cell Biology and Physiology and Orthopaedic Surgery Washington University School of Medicine 510 South Kingshighway, St. Louis, MO, USA 63110 rcivitel@im.wustl.edu.
REFERENCES
- 1.Food and Nutrition Board . Dietary Reference Intakes (DRI) for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride.: Food and Nutrition Board (FNB), Institute of Medicine. National Academy Press; Washington, DC: 1997. p. 253. [Google Scholar]
- 2.Heaney RP. The importance of calcium intake for lifelong skeletal health. Calcif Tissue Int. 2002a;70(2):70–3. doi: 10.1007/s00223-001-0032-3. [DOI] [PubMed] [Google Scholar]
- 3.Lips P. Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr Rev. 2001;22(4):477–501. doi: 10.1210/edrv.22.4.0437. [DOI] [PubMed] [Google Scholar]
- 4.Papadimitropoulos E, Wells G, Shea B, et al. Meta-analyses of therapies for postmenopausal osteoporosis. VIII: Meta-analysis of the efficacy of vitamin D treatment in preventing osteoporosis in postmenopausal women. Endocr Rev. 2002;23(4):560–9. doi: 10.1210/er.2001-8002. [DOI] [PubMed] [Google Scholar]
- 5.Shea B, Wells G, Cranney A, et al. Meta-analyses of therapies for postmenopausal osteoporosis. VII. Meta-analysis of calcium supplementation for the prevention of postmenopausal osteoporosis. Endocr Rev. 2002;23(4):552–9. doi: 10.1210/er.2001-7002. [DOI] [PubMed] [Google Scholar]
- 6.Food and Nutrition Board . Dietary Reference Intakes (DRI) for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride.: Food and Nutrition Board (FNB), Institute of Medicine. National Academy Press; Washington, DC: 1997. pp. 115–7.pp. 273–5. [Google Scholar]
- 7.Food and Nutrition Board . Dietary Reference Intakes (DRI) for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride.: Food and Nutrition Board (FNB), Institute of Medicine. National Academy Press; Washington, DC: 1997. pp. 388–9. [Google Scholar]
- 8.Dawson-Hughes B, Heaney RP, Holick MF, et al. Estimates of optimal vitamin D status. Osteoporosis International. 2005;16(7):713–6. doi: 10.1007/s00198-005-1867-7. [DOI] [PubMed] [Google Scholar]
- 9.NOF . National Osteoporosis Foundation’s Updated Recommendations for Calcium and Vitamin D intake. National Osteoporosis Foundation; 2007. http://www.nof.org/prevention/calcium_and_VitaminD.htm. [Google Scholar]
- 10.Dietrich T, Joshipura KJ, Dawson-Hughes B, Bischoff-Ferrari HA. Association between serum concentrations of 25-hydroxyvitamin D3 and periodontal disease in the US population. Am J Clin Nutr. 2004;80(1):108–13. doi: 10.1093/ajcn/80.1.108. [DOI] [PubMed] [Google Scholar]
- 11.Heaney RP. Barriers to optimizing vitamin D3 intake for the elderly. Journal of Nutrition. 2006;136(4):1123–5. doi: 10.1093/jn/136.4.1123. [DOI] [PubMed] [Google Scholar]
- 12.Nishida M, Grossi SG, Dunford RG, et al. Calcium and the risk for periodontal disease. J Periodontol. 2000;71(7):1057–66. doi: 10.1902/jop.2000.71.7.1057. [DOI] [PubMed] [Google Scholar]
- 13.Frost HM. Bone Remodeling and Its Relationship to Metabolic Bone Disease. Charles C. Thomas; Springfield, Ill: 1973. Remodeling as a determinant of envelope physiology; pp. 28–53. [Google Scholar]
- 14.Cannell JJ, Zasloff M, Garland CF, Scragg R, Giovannucci E. On the epidemiology of influenza. Virol J. 2008;5:29. doi: 10.1186/1743-422X-5-29. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Gombart AF, Borregaard N, Koeffler HP. Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3. Faseb J. 2005;19(9):1067–77. doi: 10.1096/fj.04-3284com. [DOI] [PubMed] [Google Scholar]
- 16.Levin RI, Rubin DS. Applied Elementary Statistics. Prentice-Hall, Inc.; Englewood Cliffs, New Jersey: 1980. [Google Scholar]
- 17.Hildebolt CF, Pilgram TK, Dotson M, et al. Attachment loss with postmenopausal age and smoking. J Periodontal Res. 1997;32(7):619–25. doi: 10.1111/j.1600-0765.1997.tb00940.x. [DOI] [PubMed] [Google Scholar]
- 18.Villareal DT, Civitelli R, Chines A, Avioli LV. Subclinical vitamin D deficiency in postmenopausal women with low vertebral bone mass. J Clin Endocrinol Metab. 1991;72(3):628–34. doi: 10.1210/jcem-72-3-628. [DOI] [PubMed] [Google Scholar]
- 19.Holick MF. Resurrection of vitamin D deficiency and rickets. Journal of Clinical Investigation. 2006;116(8):2062–72. doi: 10.1172/JCI29449. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Murakami M, Ohtake T, Dorschner RA, Gallo RL. Cathelicidin antimicrobial peptides are expressed in salivary glands and saliva. J Dent Res. 2002;81(12):845–50. doi: 10.1177/154405910208101210. [DOI] [PubMed] [Google Scholar]
- 21.Wang TT, Nestel FP, Bourdeau V, et al. Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol. 2004;173(5):2909–12. doi: 10.4049/jimmunol.173.5.2909. [DOI] [PubMed] [Google Scholar]
- 22.Cannell JJ, Vieth R, Umhau JC, et al. Epidemic influenza and vitamin D. Epidemiology & Infection. 2006;134(6):1129–40. doi: 10.1017/S0950268806007175. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Liu PT, Stenger S, Li H, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response.[see comment] Science. 2006;311(5768):1770–3. doi: 10.1126/science.1123933. [DOI] [PubMed] [Google Scholar]
- 24.Zittermann A. Vitamin D in preventive medicine: are we ignoring the evidence? Br J Nutr. 2003;89(5):552–72. doi: 10.1079/BJN2003837. [DOI] [PubMed] [Google Scholar]
- 25.Hildebolt C. Effect of Vitamin D and Calcium on Periodontitis. Journal of Periodontology. 2005;76:1576–1587. doi: 10.1902/jop.2005.76.9.1576. [DOI] [PubMed] [Google Scholar]
- 26.Takaishi Y, Miki T, Nishizawa Y, Morii H. Clinical effect of etidronate on alveolar pyorrhoea associated with chronic marginal periodontitis: report of four cases. J Int Med Res. 2001;29(4):355–65. doi: 10.1177/147323000102900413. [DOI] [PubMed] [Google Scholar]
- 27.Jeffcoat MK, Reddy MS. Alveolar bone loss and osteoporosis: Evidence for a common mode of thearpy using the bisphoshonate alendronate. In: Davidovitch Z, Norton L, editors. The Biologic Mechanism of Tooth Resorption and Replacement by Implants. Harvard Society for the Advancement of Orthodontics; Boston: 1996. pp. 365–373. [Google Scholar]
- 28.Rocha M, Nava LE, Vazquez de la Torre C, et al. Clinical and radiological improvement of periodontal disease in patients with type 2 diabetes mellitus treated with alendronate: a randomized, placebo-controlled trial. J Periodontol. 2001;72(2):204–9. doi: 10.1902/jop.2001.72.2.204. [DOI] [PubMed] [Google Scholar]
- 29.Lane N, Armitage GC, Loomer P, et al. Bisphosphonate therapy improves the outcome of conventional periodontal treatment: results of a 12-month, randomized, placebo-controlled study. J Periodontol. 2005;76(7):1113–22. doi: 10.1902/jop.2005.76.7.1113. [DOI] [PubMed] [Google Scholar]
- 30.Marx RE, Sawatari Y, Fortin M, Broumand V. Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg. 2005;63(11):1567–75. doi: 10.1016/j.joms.2005.07.010. [DOI] [PubMed] [Google Scholar]
- 31.Migliorati CA, Schubert MM, Peterson DE, Seneda LM. Bisphosphonate-associated osteonecrosis of mandibular and maxillary bone: an emerging oral complication of supportive cancer therapy. Cancer. 2005;104(1):83–93. doi: 10.1002/cncr.21130. [DOI] [PubMed] [Google Scholar]
- 32.Grbic JT, Landesberg R, Lin SQ, et al. Incidence of osteonecrosis of the jaw in women with postmenopausal osteoporosis in the health outcomes and reduced incidence with zoledronic acid once yearly pivotal fracture trial. J Am Dent Assoc. 2008;139(1):32–40. doi: 10.14219/jada.archive.2008.0017. [DOI] [PubMed] [Google Scholar]
- 33.Payne JB, Zachs NR, Reinhardt RA, Nummikoski PV, Patil K. The association between estrogen status and alveolar bone density changes in postmenopausal women with a history of periodontitis. J Periodontol. 1997;68(1):24–31. doi: 10.1902/jop.1997.68.1.24. [DOI] [PubMed] [Google Scholar]
- 34.Krall EA, Dawson-Hughes B, Hannan MT, Wilson PW, Kiel DP. Postmenopausal estrogen replacement and tooth retention. Am J Med. 1997;102(6):536–42. doi: 10.1016/s0002-9343(97)00045-4. [DOI] [PubMed] [Google Scholar]
- 35.Paganini-Hill A. The benefits of estrogen replacement therapy on oral health. The Leisure World cohort. Arch Intern Med. 1995;155(21):2325–9. [PubMed] [Google Scholar]
- 36.Civitelli R, Pilgram TK, Dotson M, et al. Hormone/estrogen replacement therapy improves alveolar and postcranial bone density in postmenopausal women. Archives of Internal Medicine. 2002 doi: 10.1001/archinte.162.12.1409. [DOI] [PubMed] [Google Scholar]
- 37.Food and Nutrition Board . Dietary Reference Intakes (DRI) for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride.: Food and Nutrition Board (FNB), Institute of Medicine. National Academy Press; Washington, DC: 1997. [Google Scholar]