Bone Active Periodontitis Treatments: Effects of Vitamin D and Calcium C. HILDEBOLT 1, N. GARCIA 2, D. DIXON 3, D.D. MILEY 2, R. COUTURE 1 C., W. SHANNON 1, MUELLER 1, E. LANGENWALTER 3, C. ANDERSON 1, and R. CIVITELLI 1, 1 Washington University, Saint Louis, MO, USA, 2 Saint Louis University, MO, USA, 3 Southern Illinois University, Alton, USA

Background and Objective In periodontal disease, the inflammatory response to pathogenic periodontal microbes results in connective-tissue breakdown and alveolar bone resorption. Low dietary intakes of vitamin D and calcium hasten bone loss and osteoporosis. Vitamin D metabolites suppress the inflammatory response and stimulate production of natural antibiotics. Objective: To determine the extent to which measurements of periodontal disease vary between two groups of patients who do and do not take vitamin D and calcium oral supplementation.

Subjects and Methods From June 2007 to February 2008 fifty-one (51) subjects receiving periodontal maintenance therapy were recruited from 2 dental clinics. Subjects were: Women ≥ 5 years postmenopausal and men ≥ 50 years old In good medical health, No condition nor medication that would affect periodontal or bone health Subjects had ≥ 2 interproximal sites with ≥ 3 mm clinical attachment loss Defined for study as moderate to severe chronic periodontal disease Armitage GC (1999) Development of a classification system for periodontal diseases and conditions. Ann Periodontol 4:1-6.)

Methods For mandibular posterior teeth the following data were entered into computer memory at chairside: Probing Depth, Attachment loss, Probing measurements made repeated until agreement to within 1 mm Gingival Index (Loe, 1967), score 0-3, Bleeding on Probing (yes-no), Calculus Index (Greene, 1967), score 0-3, Plaque Index (Loe, 1967), score 0-3, Furcation Involvement (Glickman, 1953), (score I - IV).

Methods: radiographic image acquisition Two new standard intraoral phosphor plates assigned to each subject Customized, occlusal registration device constructed for each subject Three types of measurements of alveolar bone: Two of alveolar crest height One of change in X-ray transmission.

Alignment Device

Cemento-enamel-junction-alveolar-crest (CEJAC) measurements High-pass-filtered image, features > 40 pixels removed. (High-pass image sometimes adds clarity to edge of bone.)

Simulated crest change of mm Images registered by minimizing trabecular noise

Simulated crest change of mm

Simulated crest change of mm

Simulated crest change of mm

Regions of interest (ROIs) and reference ROIs used for transmission measurements The difference in transmission measurements is proportional to change in bone mass

Methods Daily calcium and vitamin D intakes (from food and supplements) estimated by nutritional analysis. Each subject receives dental prophylaxis and oral-hygiene instruction at baseline and every three months Data collected at baseline and 6 months Repeated-measures, multivariate analysis of variance used to analyze baseline data

Twenty-three (23) subjects in taker group ≥400 international units (IUs)/day of vitamin D and ≥1000mg/day of calcium One taker had a calcium intake of 897 mg/day Retained in study Twenty-eight (28) subjects were in the non-taker group Five non-takers had dietary intakes of calcium >1000 mg/day (1551, 1180, 1157, 1079, and 1066 mg/day) Retained in study, but 5 additional non-takers added One non-takers had vitamin D intake of 417/day Retained in study Average age: takers = 63.9 years; non-takers = 62.0 Six-month data available for 22 takers and 26 non-takers Results

Takers Non-takers Mean values and 95% confidence intervals. Measurement Calcium intake Vitamin D intake Taker (n=23) 1769 ( ) mg/day 1049 ( ) IU/day Non-taker (n=28) 642 ( ) mg/day 156 ( ) IU/day

Results Pocket depth Attachment loss ∆ = 13% ∆ = 20% ∆ = 13% ∆ = 9% ∆ = 21% ∆ = 17% ∆ = 13 % Taker Non-taker

Results Bleeding sites Gingival index ∆ = 28% ∆ = 27 % ∆ = 29% ∆ = 13% ∆ = 17% ∆ = 21% ∆ = 9% Taker Non-taker

Results Calculus index Plaque index ∆ = 18% ∆ = 0% ∆ = 1 % ∆ = 13% ∆ = 85% ∆ = -22% ∆ = 73% ∆ = 30 % Taker Non-taker

Results Month 0 CEJ-AC Radiographic Furcation index ∆ = -5% ∆ = 36% ∆ = -6 % ∆ = 37% ∆ = 16% Taker Non-taker

Results Six-month alveolar crest change by subtraction radiography 0.01 mm gain both groups Six-month alveolar bone readiodensity change by subtraction radiography 1% decrease non-takers For baseline data, repeated-measures, multivariate analysis of variance indicated that differences (when considered collectively) were borderline statistically significant (p = 0.08)

Discussion A limitation of our study is that serum levels of 25- hydroxyvitamin D (the best index of a subject’s vitamin D status) were not known for our subjects Serum 25 hydroxyvitamin D levels increase ∼ 0.70 nmol/l for each μg (40 IU) of vitamin D supplementation Difference between takers and non-takers = 905 IU/day Would raise 25-hydroxyvitamin D serum levels only by about 15 nmol/l (6 ng/ml) Population in our area = 58.9 nmol/L (23.6 ng/ml) Beneficial effects of vitamin D flatten at 100 to 110 nmol/L (40-44 ng/ml) 25-hydroxyvitamin D out Populations in sun-rich environments = nmol/L ( ng/ml)

Discussion Doses (in addition to normal intakes from sunshine, diet, and supplementation) in randomized control trials should be 2,000 to 10,000 IU/day Doses of 3,800 to 5,000 IU/day of vitamin D 3 required to ensure that vitamin D deficiency or insufficiency resolved in more than 80% of supplemented people In spite of our efforts, only 3 subjects had diet plus oral- supplementation intakes of vitamin D > 2000 IU/day (2237, 2324, and 2654 IU/day), with a mean vitamin D intake of 1049 IU/day

Discussion Current recommendation for calcium intake is 1200 mg/day for ages over 50 Takers = 1769 mg/day--below the tolerable upper intake level (2500 mg/day) Non-takers = 642 mg/day--below the tolerable upper intake level (2500 mg/day) In the U.S., the median calcium intake For men 50 to 70 years of age = 708 mg/day For women 571 mg/day. Over the age of 70, the respective median intakes are 702 and 517 mg/day.

Discussion We surveyed of 204 patients > 50 years of age in our periodontal recall programs, Only 15(7%) met the U.S. Food and Nutrition Board’s recommended intake levels for calcium and vitamin D through oral supplementation. The recommendation for vitamin are supposedly adequate for preventing ostomalacia in adults

Conclusion These preliminary, observational data are consistent with the notion that vitamin D and calcium supplementation may be helpful in the management of periodontal disease patients.

Acknowledgement Study supported by USPHS grants R21 DE and UL1 RR024992