|Year : 2016 | Volume
| Issue : 4 | Page : 286-290
Low serum 1,25(OH) 2 D levels: A risk factor for periodontitis
Rajashree Dasari, Veerendranath Reddy Panthula, Sandeep Nandakumar, Rekha Rani Koduganti, Himabindu Gireddy, Sangeeta Sehrawat
Department of Periodontics, Panineeya Mahavidhyalaya Institute of Dental Sciences and Research Centre, Hyderabad, Telangana, India
|Date of Web Publication||23-Dec-2016|
Panineeya Mahavidhyalaya Institute of Dental Sciences and Research Centre, Road No. 5, Kamala Nagar, Dilsukhnagar, Hyderabad - 500 060, Telangana
Source of Support: None, Conflict of Interest: None
Context: Vitamin D has been associated with bone health and it is well understood that vitamin D deficiency leads to various disorders. 1,25(OH) 2 D maintains oral health through its effect on bone and mineral metabolism and innate immunity.
Aims: The aim was to evaluate the association between serum levels of 25-hydroxyvitamin D [25(OH)D] and 1,25(OH) 2 D and periodontal disease risk and also the effect of low serum levels on periodontal surgical outcomes in periodontitis patients.
Settings and Design: The study was designed as a case control clinical trial that was conducted to identify the risk of low levels of serum vitamin D in progression of the disease and also in periodontal healing process.
Materials and Methods: A total of 51 chronic periodontitis patients and 33 periodontally healthy subjects were included in the study. The serum levels of both 25(OH)D and 1,25(OH) 2 D were determined. Parameters, such as plaque index, bleeding on probing (BOP), clinical attachment level (CAL), and pocket depth (PD), were measured at baseline, 6 weeks, and 6 months to assess the periodontal status.
Statistical Analysis Used: The data were analyzed using chi-square test, independent sample t-test, repeated measures analysis of variance (ANOVA) with post hoc Bonferroni test.
Results: There was statistically significant association between serum 1,25(OH) 2 D level and periodontal health status (12.73 ± 4.19 vs. 20.36 ± 5.50). The subjects with chronic periodontitis showed low serum levels of 1,25(OH) 2 D, and individuals with severe deficiency have shown less clinical attachment gain and PD reduction when compared with minimal deficiency patients after the surgery.
Conclusions: Analysis of these data suggest that low serum 1,25(OH) 2 D level seem to be associated with chronic periodontitis and 1,25(OH)2D deficiency negatively affects the periodontal surgical treatment outcome.
Keywords: Chronic periodontitis, periodontal surgical outcome, vitamin D
|How to cite this article:|
Dasari R, Panthula VR, Nandakumar S, Koduganti RR, Gireddy H, Sehrawat S. Low serum 1,25(OH) 2 D levels: A risk factor for periodontitis. J NTR Univ Health Sci 2016;5:286-90
|How to cite this URL:|
Dasari R, Panthula VR, Nandakumar S, Koduganti RR, Gireddy H, Sehrawat S. Low serum 1,25(OH) 2 D levels: A risk factor for periodontitis. J NTR Univ Health Sci [serial online] 2016 [cited 2020 Apr 10];5:286-90. Available from: http://www.jdrntruhs.org/text.asp?2016/5/4/286/196589
| Introduction|| |
Periodontitis is a multifactorial disease condition resulting from interaction between various pathogens and host response. The interaction triggers events of complex inflammatory process, which in turn leads to tissue destruction and remodeling of alveolar bone.
Vitamin D is a host-derived molecule formed in the skin by ultraviolet radiation. It is activated by metabolism in the liver and gets converted to 25-hydroxyvitamin D [25(OH)D], which has biologically less functions than the most active form, i.e. 1,25-hydroxyvitamin D [1,25(OH) 2 D].  These molecules bind to vitamin D receptor (VDR) and serves as a nuclear transcription factor, altering gene function and inducing protein synthesis. Directly or indirectly, 1,25(OH) 2 D regulates over 200 genes. ,,
Most of the previous studies showed association between high serum levels of 25(OH)D with periodontal health and treatment, ,,, whereas a few studies reported mild protective effect on periodontal health by vitamin D supplements. , Another study reported a trend toward an increased systemic 25(OH)D level after scaling and root planning in chronic periodontitis patients.  All the above studies measured the level of serum 25(OH)D, presenting the circulating storage form of vitamin D. But 1,25(OH) 2 D is known to be the active form that exerts most of the biological functions of vitamin D. 1,25(OH) 2 D plays an important role in maintaining calcium and phosphate levels in blood by stimulating intestinal absorption and bone resorption.  Hence, it is reasonable to expect this effect on alveolar bone in 1,25(OH) 2 D deficient patients. To further explore the role of 1,25(OH) 2 D in periodontitis, the present study was performed to investigate the possible association of serum 25(OH)D and 1,25(OH) 2 D levels with periodontal health status and also to evaluate the effect of low levels of serum 1,25(OH) 2 D on periodontal surgical outcomes.
| Materials and methods|| |
The patients with chronic periodontitis were selected from among those referred to the Department of Periodontics, of a tertiary referral care hospital, Hyderabad, India. Institutional review board approved the present study and all participants gave written informed consent. The subjects under periodontal therapy within previous 3 months, patients on drugs for vitamin D or calcium supplements, pregnant subjects, smokers and patients with systemic diseases were excluded from the study.
There were total of 51 patients with periodontitis of varying degrees and 33 periodontally and systematically healthy control subjects who reported to the department for oral prophylaxis. The patient's characteristics are presented in [Table 1].
Clinical periodontal examination
Periodontal measurements were performed at mesiobuccal, distobuccal, midbuccal, and mid-palatal of fully erupted teeth excluding third molars. Clinical parameters, such as plaque, probing depth, and clinical attachment loss, were measured. The score for bleeding (present/absent) was registered after probing. Mechanical periodontal therapy, such as scaling and root planning, was performed including oral hygiene education. These treatments were repeated and 51 periodontitis patients received open flap debridement wherever indicated. Reexamination of above parameters was done at 6 weeks and 6 months after the completion of the treatment.
Blood samples were collected from both 51 periodontitis group and 33 healthy controls. Serum was obtained by centrifugation and stored at −70°C until analysis. Serum concentrations of 25(OH)D were measured using commercially available 25(OH)D EIA kit and 1,25(OH) 2 D by 1,25(OH) 2 D RIA kit according to the manufacturer's instructions [both from Immunodiagnostic systems limited, UK]. The data of 25(OH)D and 1,25(OH) 2 D are expressed as nanograms and picograms per milliliter, respectively. The assays have wide measuring ranges: 0-160 ng/mL for 25(OH) D and 0-210 pg/mL for 1,25(OH) 2 D.
| Results|| |
All the statistical analysis was done using Statistical Package for the Social Sciences (SPSS) version 16 (SPSS-Inc., Chicago, IL). A P-value of <0.05 was considered statistically significant. Comparison of categorical variables was done using Chi-square test. Intergroup comparisons of continuous variables were done using independent sample t test, and intragroup was done using repeated measures analysis of variance (ANOVA) with post hoc Bonferroni test.
Demographic characteristics of patients and serum concentration level of 25(OH)D and 1,25(OH) 2 D are given in [Table 1]. The mean age of the participants in the test group was 46.16 years and in control group was 37.26 years. Males and females are almost equally distributed in both the groups. The parameters, such as plaque index, bleeding on probing (BOP), pocket depth (PD) >4 mm, and AL >4 mm, were almost of similar range in all diseased patients.
No universally accepted values for vitamin D deficiency status are given. The normal range of serum vitamin D levels is 20-74 ng/mL. According to most of authors, levels below 30 ng/mL is considered to be insufficient, with severe deficiency beginning at a level of 12 ng/mL.  Majority of subjects in both test and control group were 1,25(OH) 2 D deficient. Twenty-two chronic periodontitis patients and 3 subjects from the control group had severe deficiency. Forty-nine percent of periodontitis and 15% of healthy patients showed insufficient levels of 1,25(OH) 2 D. When compared to the serum levels of 25(OH)D, periodontally healthy subjects showed higher mean concentration than the chronic periodontitis patients but was not statistically significant [23.34 ± 4.94 vs. 24.56 ± 4.82, P > 0.001]. There was inverse correlation between serum levels of 1,25(OH) 2 D and periodontal health, while 25(OH)D was not associated with the progression of the disease [Table 1].
When intragroup comparison was made among the test groups, individuals who have insufficient or mild deficiency levels of 1,25(OH) 2 D showed 1.23% greater CAL and 3% more PD reduction than the patients with severe deficiency, at 6-week follow-up after the surgery. At 6 months, the outcomes for vitamin D-deficient and -insufficient participants were similar for PD [4.01 mm vs. 3.79 mm], whereas CAL increased by 3.4 mm in individuals with insufficient levels. However, significant difference in clinical outcomes between deficient and insufficient individuals were noted at both follow-up points [Table 2], [Figure 1] and [Figure 2].
|Figure 1: Pocket depth reduction. Clinical outcomes of vitamin-D insufficient and deficient participants treated with periodontal flap surgery. Mean changes from baseline to 6 months for probing depth reduction (I), clinical attachment level gain (II)|
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|Figure 2: Clinical attachment level gain. Clinical outcomes of vitamin-D insufficient and deficient participants treated with periodontal flap surgery. Mean changes from baseline to 6 months for probing depth reduction (I), clinical attachment level gain (II)|
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|Table 2: Correlation between probing depth (PD) and attachment loss (AL) at various time intervals before and after periodontal surgery|
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| Discussion|| |
This study shows a positive association between low serum levels of 1,25(OH) 2 D and periodontal disease status. The periodontitis group showed significantly lower level of 1,25(OH) 2 D [12.73 pg/mL] than periodontally healthy group [20.36 pg/mL]. In contrast to serum 25(OH)D level where there is no association with periodontal disease.
Analysis of cross-sectional data from the third National Health and Nutrition Examination Survey (NHANES III) revealed that individuals with the highest 25(OH)D levels experienced 20% less BOP than those with the lowest levels, suggesting that vitamin D may reduce the risk of gingival inflammation by exerting anti-inflammatory effects. 
Analysis of data from this study also demonstrated an inverse relationship between clinical attachment loss (CAL) and 25(OH)D levels in persons aged 50 years or older.  Likewise many previous studies on chronic disease determine only 25(OH)D levels although the active metabolite is 1,25(OH) 2 D that plays a key role in disease pathogenesis.
At molecular level, 1,25(OH) 2 D 3 modulates gene expression through a heterodimer between VDR and retinoid X receptor by acting as a ligand. In the absence of this ligand, most of VDR remain in the cytoplasm,  thereby hamapering the positive effects of 1,25(OH) 2 D 3 .
The association between 1,25(OH) 2 D with periodontal disease, shown in the present study may be explained by either immune modulatory effects or bone related functions. Many in vitro studies have shown anti-inflammatory effects of vitamin D such as inhibition of antigen-induced T cell proliferation and cytokine production, specifically interleukin 2 and interferon. , It also has marked effects on antigen presenting cells. ,
In a small randomized clinical trial of critically ill patients in the intensive care unit, supplementation with 500 IU parenteral vitamin D significantly decreased circulating concentrations of C-reactive protein.  In addition, many animal studies showed the beneficial effects of 1,25(OH) 2 D. However, clinical human studies evidence is scarce.
Based on the above ﬁndings, it is logical to assess that low levels of serum vitamin D could be a risk factor for the development of periodontal disease as in the present study. The chronic periodontitis patients have low serum levels of 1,25(OH) 2 D. The reason for low serum level in diseased patients might be due to its defense mechanism in fighting against the infection. Another possible explanation could be due to nonavailability of substrate but the serum 25(OH)D levels of both periodontitis and control group were similar in range. In contrast to the present study, many studies interpreted the association between 25(OH)D and periodontal health. This could be due to inadequate levels present locally. To better understand the potential role of vitamin D in periodontal disease pathogenesis, further studies of both 25(OH)D and 1,25(OH) 2 D on a local level i.e. in gingival crevicular ﬂuid or in tissue biopsies are needed which will be addressed in our future studies.
As vitamin D plays a key role in bone formation and immune regulation, the outcome of periodontal surgery have been analyzed in periodontitis patients with low levels of serum 1,25(OH) 2 D, since it is an active metabolite. In the present study, almost all the individuals of the diseased group have moderate-to-severe deficiency of 1,25(OH) 2 D. A recent survey stated that only 7% of periodontal maintenance patients had vitamin D intake level that met the published guidelines.  However, this is the first study to report the effect of serum 1,25(OH) 2 D status on periodontal surgery outcome. Individuals with mild deficiency or insufficiency resulted in greater CAL gain and PD reduction compared with severe deficiency patients. There is even further attachment loss and PD formation in both the groups by the end of 6 months.
Results from animal studies shows that vitamin D may play a predominant role in mandibular anabolic bone formation and may exert positive effects on fracture healing.  In the pre-clinical studies related to bisphosphonate-associated osteonecrosis of the jaw, compromised osseous healing in the oral cavity was observed in vitamin D deficiency patients supporting the role of vitamin D in bone healing. 
Analysis of these data suggest that individuals with adequate vitamin D levels obtain better results from open flap surgery than vitamin D-deficient individuals. Low levels could negatively affect the periodontal healing process. Since it is a 6-month study, radiographic outcomes have not been analyzed, which is a limitation of the study. However, larger sample size and longitudinal studies are needed to confirm the above results.
| Conclusion|| |
The present study concludes that a low level of serum 1,25(OH) 2 D could be a risk factor for chronic periodontitis. Since most of the individuals are vitamin D deficient, supplementation along with periodontal surgery may ensure better surgical outcome. Moreover, 1,25(OH) 2 D can be used as a marker for disease progression. Further studies on this aspect can be helpful to prove the efficacy of vitamin D in treating periodontal disease.
The authors would like to thank all the staff of the Department of Periodontics, Panineeya Mahavidyalaya Institute Dental Sciences, Hyderabad, for facilitating the study. I also thank Dr. K. Sridhar Rao, Center for Cellular and Molecular Biology, Hyderabad, India, for his valuable suggestions and help rendered.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2]