This trial aimed to evaluate the efficacy and safety of vitamin D supplementation on the residual moderate and deep pockets following nonsurgical periodontal therapy.

2. EFFECT OF SHORT-TERM VITAMIN D
SUPPLEMENTATION AFTER NONSURGICAL
PERIODONTAL TREATMENT: A RANDOMIZED,
DOUBLEMASKED, PLACEBO-CONTROLLED
CLINICAL TRIAL
Weimin Gao; Huilin Tang; Danyang Wang; Xuan Zhou;
Yiqing Song; Zuomin Wang
Presented By:
BEENA VIJAYAN PARVATHY

3. This trial aimed to evaluate the efficacy and safety of
vitamin D supplementation on the residual moderate and
deep pockets following nonsurgical periodontal therapy.

4.  Periodontitis is one of the most common chronic inflammatory
diseases with an overall prevalence ranging from 10% to 90% in
adults.
 If untreated, periodontitis may lead to loss of teeth and ultimately
result in edentulism, which has been shown to have a negative
impact on an individual's quality of life.
 Vitamin D is classified as a secosteroid in which one of the rings
has been broken by ultraviolet B (UVB) sunlight and the main
source of vitamin D is de novo synthesis in the skin.
 It is well known for its role in calcium homeostasis by
promoting calcium absorption in the intestine and stimulating
osteoblasts to enable normal bone growth and preservation.

5. RATIONALE OF THE STUDY
VITAMIN D AND PERIODONTAL HEALTH
 More recent studies showed significant associations between
periodontal health and intake of vitamin D and calcium, and that
dietary supplementation with calcium and vitamin D may
improve periodontal health, increase bone mineral density in the
mandible and inhibit alveolar bone resorption.
 In a recently published longitudinal study, Garcia et al reported
that calcium and vitamin D supplementation may reduce the
severity of periodontal disease if used at doses higher than 800-
1,000 IU daily and supported the rational for testing the potential
beneficial role of vitamin D on periodontal disease in randomized
clinical trials.

6.  They also noted that vitamin D, in addition to its role in bone and
calcium homeostasis, acts as an anti-inflammatory agent because
it inhibits immune cell cytokine expression and causes
monocyte/macrophages to secrete molecules that have a strong
antibiotic effect. Indeed, vitamin D deficiency may be linked to
increased risk of infectious diseases.
 This suggests that vitamin D may be of benefit in the treatment
of periodontitis, not only because of its direct effects on bone
metabolism, but also because it may have antibiotic effects on
periodontopathogens and inhibit inflammatory mediators that
contribute to the periodontal destruction.

7.  Recent research indicates that with the help of certain enzymes,
gingival epithelial cells can convert inactive vitamin D (Vitamin
D3) to the active form (25(OH)D) in situ, which could have local
effect on periodontal tissue directly.
 Menzel LP et al reported that treatment of gingival epithelial
cells with 25(OH)D inhibited the intracellular growth of P
gingivalis.
 Topical application of both vitamin D3 and 25(OH)D to the
gingiva of mice led to rapid inhibition of IL-1α expression, a
prominent pro-inflammatory cytokine associated with
inflammation.

8.  Liu K et al found that 25(OH)D concentrations in gingival
crevicular fluid were 300 times higher than those in the plasma of
patients with aggressive periodontitis.
 Several observational studies reported that vitamin D levels were
inversely associated with gingivitis and periodontitis.
 Additionally, vitamin D and calcium supplementation had a
modest positive effect on periodontal health.

9. STUDY DESIGN
 This study was a one-center, randomized placebo-controlled,
double-blind parallel trial with 3 months of follow-up.
 This study design included a pre-study phase of 3-month clinical
examination to screen patients and 3 months of interventional
period.
 Patients with chronic periodontitis were screened and recruited
from the Department of Stomatology, Beijing Chao-Yang
Hospital, Capital Medical University between December 2014
and June 2015.

10. After 3 months of periodontal examination.
INCLUSION CRITERIA
 Age between 30 and 70 years old.
 More than 20 teeth remaining in the mouth.
 Clinical diagnosis of moderate to severe periodontits.
 Not receiving periodontal treatment within last 6 months.
 Not taking antibiotic drugs within the previous 3 months.
DIAGNOSTIC CRITERIA
 For moderate to severe periodontitis.
At least six sites for all teeth in the mouth with periodontal pocket
depth more than 6 mm, attachment loss(AL) more than 4 mm.
X-ray showing at least six sites with alveolar bone loss more than
one third of the root length.

11. EXCLUSION CRITERIA
 Diabetes, thyroid, or parathyroid endocrine-associated diseases.
 Severe systemic diseases, such as cancer.
 Taking vitamin D and/or calcium drugs during the pre-study
phase.
 Taking aspirin, non-steroidal anti-inflammatory drugs, or
steroids.
 Pregnant or preparing to become pregnant within the previous
year.
 Suffering from hypercalcemia and malabsorption syndrome.
STUDY POPULATION
The number of patients to be enrolled per group was calculated to
be 99. However, taking into account a possible dropout rate of
<20%, the final number of patients included in this trial was 120.

12. CLINICAL PROCEDURES
 In the pre-study phase, patients‘ were collected with basic
information, including age, sex, height, weight, smoking history,
and preliminary periodontal status (eg, tartar, plaque, and stain).
 All subjects were assigned to receive periodontal therapy
including oral hygiene instruction, supragingival scaling,
subgingival scaling, and root planing.

13. • Periodontal examinations were performed with Williams probe
one week after supragingival scaling to record plaque index (PLI),
probing depth (PD), bleeding index (BI), AL, tooth loss, and tooth
mobility.
•All patients received the same treatment procedures throughout
the study.
•After three months of nonsurgical periodontal therapy, clinical
examination was performed to select eligible patients.
•A total of 360 patients were randomly assigned to receive a
pillpack containing 90 capsules of 2000 IU vitamin D3, 1000 IU
vitamin D3, or placebo.

14.  Participants were instructed to take one capsule daily and not to
provide any information to the study personnel about the
treatment assignments.
 During the periods of intervention, the subjects were followed
up every month and asked to bring back the pillpacks.
 Three months after the intervention, all subjects were followed
up at clinical visits and underwent periodontal examinations.
 If the patients’ PD measurements ≥6 mm during follow-up,
periodontal surgery was suggested for those sites.

15.  The primary outcome measure was AL, and the secondary
outcome measures included serum 25(OH)D levels, ACH, PD,
BI, and PLI.
 Serum 25(OH)D levels were measured by vitamin D Direct Elisa
kit (Immunodiagnostic Systems Limited, IDS). To measure
serum 25(OH)D levels, 3 mL venous blood samples were drawn
by venipuncture after a 12-hours fast. After 1 hour coagulation,
serum was centrifuged and stored at −20°C.
 Examinations of PD and AL included six sites on each tooth:
mesial buccal, buccal, distal buccal, mesial lingual, lingual, and
distal lingual.

16.  Panoramic radiographs derived from CBCT data were used to
evaluate alveolar crest height (ACH).
 The ACH is defined as the mean of the two-dimensional vertical
distance between mesial and distal alveolar crest to apical point.
 BI was scored on a 0-5 scale when any visual evidence of
bleeding was noted.
 PLI was scored on a 0-3 scale based on the method promoted by
Silness & Löe.

17. Statistical analysis
 The normality of data distribution using the KolmogorovSmirnov
goodness-of-fit test, and data were expressed as mean ± standard
deviation (SD) for normally distributed continuous variables.
 One-way analysis of variance (ANOVA) and NeumanKeuel test
were carried out to determine difference between groups and
changes during follow-up.

18.  The last observation carried forward (LOCF) approach was used
to impute missing efficacy values.
 All statistical analysis was performed using SPSS software
(version17.0; SPSS Inc).
 A P value of P < .05 was considered statistically significant.

19. RESULTS
 Total of 360 randomized patients, 323 patients finished the
therapy regime (vitamin D 2000 IU/d: n = 105; vitamin D 1000
IU/d: n = 110; placebo: n = 108). Thirty-seven patients withdrew,
giving a dropout rate of 10.3%.
 There was a slight but significant decrease in AL and PD in both
vitamin D groups compared with placebo group for moderate and
deep pockets.

20.  About 2000 IU/d vitamin D3 group, 1000 IU/d vitamin D3
group, and placebo group all decreased the AL for both moderate
pockets (−0.4 mm vs −0.4 mm vs −0.3 mm) and deep pockets
(−1.1 mm vs −1.1 mm vs −1.0 mm) (all P < .05). Similarly, PD
was also decreased in these three groups for both moderate
pockets and deep pockets (all P < .05). In addition, vitamin D
supplementation was well tolerated, and no adverse events were
reported.

22. Baseline characteristics
Baseline characteristics of the participants
2000 IU/d
vitamin D (n
= 120)
1000 IU/d
vitamin D
(n = 120)
Placebo (n
= 120)
P-
value
Age, mean
(sd)
49 (5.4) 51 (6.3) 53 (5.2) 0.233
Gender, N (%)
Male 59 (49.2) 62 (51.6) 57 (47.5) 0.548
Female 61 (50.8) 58 (48.4) 63 (52.5) 0.632
Smoking, N
(%)
Smoker 13 (10.8) 11 (9.2) 9 (7.5) 0.374
Non-smoker 96 (80.0) 102 (85.0) 99 (82.5) 0.628
Past smoker 11(9.2) 7 (5.8) 12 (10.0) 0.541

23. Treatment effects
 After 3 months of vitamin D supplementation treatment, there
was a dose-dependent decrease in the AL and PD for moderate
and deep pockets.
 Vitamin D 2000 IU/d and 1000 IU/d provided a reduction in AL,
decreased 0.4 mm in both intervention groups on average,
compared with 0.3 mm in placebo group for moderate pockets (P
< .05); 1.1 mm in both intervention groups compared with 1.0
mm in placebo group for deep pockets (P < .05).

24.  PD was also significantly decreased: by 0.5 mm and 0.3 mm in
vitamin D intervention groups and 0.2 mm in placebo groups for
moderate pockets (P < .05); 0.6 mm and 0.5 mm in vitamin D
intervention groups and 0.4 mm in placebo group for deep
pockets (P < .05).
 The differences between intervention and placebo groups were
0.3 mm and 0.1 mm for moderate pockets; 0.2 mm and 0.1 mm
for deep pockets, which were also statistically significant
although the magnitude was modest.
 No significant difference in changes of ACH and BI was
observed between treatment groups. Besides, the differences in
mean changes of PLI were not significant among groups.

25. DISCUSSION
 Vitamin D supplementation may improve periodontal health and
may be used for treating moderate or severe periodontitis
adjunctively, which is consistent with several previous studies.
 Krall et al found that patients over 65 years old who received
supplementation of 700 IU/d vitamin D and 500 mg/d calcium
for 3 years lost fewer teeth than a placebo group.
 Hiremath et al found a dose-dependent anti-inflammatory effect
of vitamin D supplementation on gingivitis.
 Vitamin D supplementation is safe and effective anti-
inflammatory agent in doses ranging from 500 IU/d to 2000 IU/d,
with an apparent earlier effect at the highest dose of 2000 IU per
day.

26. CONCLUSION
Although statistically significant differences were observed in
favor to vitamin D supplementation, the magnitude of effect size
tended to be modest with limited clinical relevance and the long-
term efficacy and safety warrant further investigation.

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