|Year : 2020 | Volume
| Issue : 2 | Page : 107-112
Serum Iron Indices in Patients with Oral Submucous Fibrosis- A Comparative Study
KA Jassim1, BS Sreenivasan2, Deepu George Mathew MDS 3, Soma Susan Varghese1, Mayeesh Radakrishna4, T Radhika5
1 Department of Oral and Maxillofacial Pathology, Mar Baselios Dental College and Hospital, Kothamangalam, Kerala
2 Department of Oral and Maxillofacial Pathology, Annoor Dental College and Hospital, Muvatupuzha, Kerala
3 Department of Oral and Maxillofacial Pathology, Annoor Dental College and Hospital, Muvatupuzha, Kerala, India
4 Department of Oral and Maxillofacial Pathology, KMCT Dental College and Hospital, Kozhikode, Kerala
5 Department of Oral and Maxillofacial Pathology, Thai Moogambigai Dental College and Hospital, Dr MGR Educational and Research Institute University
|Date of Submission||11-Nov-2020|
|Date of Acceptance||30-Nov-2020|
|Date of Web Publication||16-Feb-2021|
Dr. Deepu George Mathew
Professor and Head, Department of Oral and Maxillofacial Pathology, Annoor Dental College and Hospital, Muvatupuzha, Kerala
Source of Support: None, Conflict of Interest: None
Introduction: Oral submucous fibrosis (OSMF) is a potentially malignant disorder whose etiopathogenesis is still under investigation. Studies have reported altered serum iron levels in patients with OSMF. Hence, iron has been proposed to play an important role in the incidence and progression of the disease. This study was undertaken to understand the role of iron in the etiopathogenesis of OSMF by estimating haemoglobin and serum iron indices (serum iron, Total iron binding capacity [TIBC], percentage transferrin saturation and serum ferritin) in subjects with OSMF. Materials and Methods: Study group comprised of patients with histopathologically confirmed OSMF (n = 30). Age and sex matched subjects with clinically normal mucosa were selected as control group (n = 15). Hemoglobin, serum ferritin, serum iron, and TIBC were estimated (Siemens Dimension RXL Max Integrated chemistry system™). Statistical analysis used: SPSSv16 was used for statistical analysis. Independent sample t test was performed to compare the values between the study group and control group. ‘p’ value less than 0.05 was considered to be statistically significant. Results: There was a significant decrease in the haemoglobin, serum iron percentage transferrin saturation, serum ferritin levels and an increase in TIBC levels in the study (OSMF) group when compared to the control group (P < 0.001). TIBC levels showed a significant (P< 0.001) increase in the study group. Among the study group 44% were in an anemic state as per the hemoglobin values. Conclusion: The findings of the present study suggest that, iron deficiency state is prevalent among patients with OSMF. This deficiency of iron has an important role in the pathogenesis and progression of this disease.
Keywords: Oral submucous fibrosis, trace element, serum iron, percentage transferrin saturation, serum ferritin, total iron binding capacity
|How to cite this article:|
Jassim K A, Sreenivasan B S, Mathew DG, Varghese SS, Radakrishna M, Radhika T. Serum Iron Indices in Patients with Oral Submucous Fibrosis- A Comparative Study. J Orofac Sci 2020;12:107-12
|How to cite this URL:|
Jassim K A, Sreenivasan B S, Mathew DG, Varghese SS, Radakrishna M, Radhika T. Serum Iron Indices in Patients with Oral Submucous Fibrosis- A Comparative Study. J Orofac Sci [serial online] 2020 [cited 2021 Mar 7];12:107-12. Available from: https://www.jofs.in/text.asp?2020/12/2/107/309586
| Introduction|| |
Oral submucous fibrosis (OSMF) is a chronic disease and a well-recognized potentially malignant disorder of the oral cavity characterized by inflammation and a progressive fibrosis of the lamina propria and deeper connective tissues. The disease is seen mostly among south east and south Asian population, particularly in the Indian subcontinent.,
The precancerous nature of OSMF was first described by Paymaster in 1956. The malignant transformation rate in oral submucous fibrosis range from 4.5% to 7.6% from different studies. The epidemiological studies on OSMF have shown a strong association with areca nut chewing. The pathologic process involved in OSMF related to fibrosis and progression into malignancy is still under investigation.
Trace elements are essential components of biological enzyme systems and structural proteins. They have been extensively studied in recent years to assess their modifying effects in the pathogenesis and progression of oral premalignant and malignant conditions. Iron as a trace element is required for the proper maturation of collagen. Various studies have shown that, fibrotic state can alter the serological iron levels. There are many reports that have analysed the levels of hemoglobin and serum iron in OSMF patients., But very few studies have evaluated other serum iron indices like serum ferritin, total iron binding capacity (TIBC) and percentage transferrin saturation.
The present study was designed to estimate and compare the levels of haemoglobin and serum iron indices (serum iron, serum ferritin, TIBC, and percentage transferrin saturation) among subjects with oral submucous fibrosis and healthy controls., The hemoglobin and serum iron indices values were also compared with various histological grades of oral submucous fibrosis within the study sample.
| Materials and Methods|| |
The study was conducted in the Department of Oral Pathology and Microbiology at Mar Baselios Dental College, Kothamangalam, Kerala. Thirty patients in the age group of 20 to 70 years with newly diagnosed and histopathologically confirmed oral submucous fibrosis are included in the study group. The histopathological diagnosis and grading of oral submucous fibrosis was made using the criteria proposed by Utsunomiya and Tillakaratne WM. Fifteen subjects within the age group of 20 to 70 years, matched in sex with those of the study group with clinically normal appearing oral mucosa were included in the control group. Subjects suffering from chronic systemic illness, defective iron metabolism, history of iron supplementation in any form in the past one year, and subjects undergoing treatment for OSMF were excluded. Ethical approval for this study (IEC/14/2012/MBDC) was provided by the Ethical Committee of Mar Baselios Dental College and Hospital, Kothamangalam, Kerala, India on 21 February 2012.
Incisional biopsy was performed in the most fibrotic area of the buccal mucosa of study group subjects in order to confirm the diagnosis and to identify the histological grade of OSMF. Five mL of fasting venous blood was drawn from the study and control group subjects. The blood was centrifuged at 1000 to 1500 rpm for 15 minutes to obtain the serum for the estimation of iron indices. Hemoglobin was assessed by Cyanmetheamoglobin method. Serum iron and TIBC were estimated by ferene method. Serum ferritin levels were measured by chemiluminescence micro particle immunoassay method. Percentage transferrin saturation was derived from TIBC and serum iron value.
Data was analysed using Statistical Package for Social Sciences (SPSS v16.0). Data were presented as Mean±SD (Standard deviation) and percentage. Independent sample t- test was performed to compare the mean serum iron, percentage transferrin saturation, TIBC, serum ferritin, and hemoglobin levels between the study group and control group. Pearson correlation was used to find the correlation between the histologic grading and different laboratory iron parameters within the study group. Post hoc analysis was done to compare the laboratory values between different grades of OSMF within the study group. P value less than 0.05 was considered to be statistically significant.
| Results|| |
Demographic data analysis
The age of study (OSMF) group patients ranged from 20 to 70 years. In our study group, 22 (73.3%) were males and 8 (26.7%) were females. All the study group patients had areca nut chewing habit. The control group consisted of 15 individuals in the age group of 20 to 70 years matched in sex with those of the study group.
Mean mouth opening was significantly lower in cases compared to controls [Figure 1].
Based on the histopathological examination, the study group was graded into early, intermediate and advanced cases.] Eight (26.7%) patients were in early stage, ten (33.3%) patients were in intermediate stage and twelve (40%) were in advanced stage of OSMF.
The mean hemoglobin value for the study subjects was 13.137±0.9583 mg/dL and for the control group was 14.867±0.52 mg/dL. There was a statistically significant reduction in the hemoglobin levels when the study group was compared with the control group (P < 0.001) [Table 1], [Figure 2].
|Table 1 Comparison of laboratory values between OSMF group and Control group|
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The percentage of anaemic subjects within the study group was 43.3% (11 males and 2 females). The hemoglobin values were within the normal limits in the control group. The hemoglobin values were also compared between different histological grades of study subjects and a decrease in hemoglobin values were noticed with an increase in the severity of grade, but without any statistically significance.
Iron-related serological indices
The mean serum iron, percentage transferrin saturation, serum ferritin levels were decreased in the study group when compared to the control group and this decrease in the serum iron indices in the study group were statistically significant (P < 0.001). The mean TIBC level was increased in the OSMF group compared to the control group and this increase was statistically significant (P < 0.001) [Table 1], [Figure 3],[Figure 4],[Figure 5],[Figure 6]. A moderate level of positive correlation was found between hemoglobin levels and mouth opening (r = 0.502).
|Figure 4 Comparison of transferrin saturation between cases and controls.|
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| Discussion|| |
OSMF is a chronic, potentially malignant disorder, commonly affecting the South and South East Asian population, especially those in the Indian subcontinent. The disease has now become an Indian epidemic with an estimated 2.5 million people being affected with this disease. The characteristic feature of the disease is submucosal fibrosis that aﬀects the oral cavity, progressively involving the pharynx and the upper esophagus. There will be burning sensation, blanching, and stiﬀening of the oral mucosa and oropharynx, leading to restricted mouth opening. This result in limited food consumption and diﬃculty in maintaining oral hygiene. The etiopathogenesis of this disease is still under investigation. The role of trace metals in the pathogenesis of various potentially malignant disorders are recognized. Many researchers have extensively studied the serologic concentrations of trace elements in OSMF.,, Trace elements like iron is involved in the maturation steps of collagen synthesis. The role of iron in the pathogenesis and progression of the disease was investigated in our study.
Low levels of hemoglobin and serum iron are suggestive of iron deficiency anemia. Decreased percentage transferrin saturation, serum ferritin and an increased TIBC value is indicative of an iron deficiency state. Serologic evaluation of hemoglobin and iron indices like serum iron, TIBC, percentage transferrin saturation and serum ferritin levels are often used as a sensitive and potentially valuable biochemical index for evaluating the role of iron in the disease process.
In our study group, 22 subjects were males and eight were females. Various epidemiological studies conducted among the Indian subjects have also shown a similar male predominance. ,,, This can be attributed to the high prevalence of areca nut chewing habit among males compared to females in India.
The age of the subjects in the study group (OSMF) ranged from 3rd to 7th decade. The studies conducted by Joshi S G  and Pindborg et al  also showed a similar age distribution. In our study group, 33% of the subjects were within the age range of 61 to 70 years. This could be because, majority (60%) of our study subjects were using betel quid rather than commercially available areca nut products. The presence of betel leaves in the quid which is proven to have antioxidant property might be the reason for the delayed incidence and progression of the disease in our study group subjects.
In the present study, mean hemoglobin and serum iron levels were significantly decreased in study group when compared to control group (P<0.00l).In our study group, 43.3% of subjects were anemic. These results are consistent with the previous studies conducted on hemoglobin status of OSMF patients. We also found that there was a moderate level of positive correlation between hemoglobin levels and mouth opening (r = 0.502). As the mouth opening decreased, the hemoglobin levels also decreased. Reduction in mouth opening in OSMF patients occur due to fibrosis of the pterygomandibular raphae region. Many studies have used mouth opening as a parameter for measuring the degree of fibrosis. In our study, we have seen that as degree of fibrosis increases, hemoglobin levels are decreasing. ,,,, The reason for the decreased hemoglobin levels among OSMF patients is attributed to increased collagen formation in the lamina propria. Iron is required for enzymes involved in the hydroxylation of proline and lysine during collagen synthesis. This hydroxylation is catalyzed by proline hydroxylase and peptidyl lysine hydroxylase. The enzyme peptidyl proline hydroxylase requires ferrous iron as cofactor. Hence, more amount of iron will be utilized for the excessive collagen synthesis in OSMF patients.
The iron absorbed from the small intestine combines with a transport globin protein in the plasma called apo transferrin. Iron combined apo transferrin is known as transferrin which is the transport form of iron. Iron is loosely bound in transferrin molecule so that iron molecules are easily released at tissue level. TIBC measures the total amount of iron transferring can bind. When there is an iron deficiency state iron binding capacity of transferrin are increased. Transferrin has an affinity for the receptors on the erythroblasts so that iron is taken into the cells by endocytosis. Iron once inside the cytoplasm of the cell combines with another protein called apo ferritin to form ferritin. So, ferritin is considered to be the storage form of iron. When the iron levels are depleted in the plasma, iron is released from these storage forms. Whenever, there is an iron deficiency there will also be an increase in TIBC levels and a decrease in the transferring and ferritin levels.,
It is a well-known fact that an iron deficiency state is established in patients even before the onset of iron deficiency anemia. Hence, along with hemoglobin values, assessment of serum iron indices reflecting the iron deficiency state is important in understanding the disease process. In the iron deficiency states, there will be a decrease of transferrin saturation (transferrin is the transport protein for iron), serum ferritin levels (storage form of iron) and increase of TIBC (reflects the free iron binding protein in serum) levels.
In this study, the mean percentage transferrin saturation, serum ferritin levels were significantly decreased in the study group compared to the control group (P < 0.001) whereas the mean TIBC level was significantly increased in the study group compared to the control group (P < 0.001) [Table 1]. All these findings demonstrate the iron deficiency state in OSMF patients.
The normal maturation of epithelium is dependent upon an iron containing enzyme, cytochrome oxidase. In iron deficiency state, low levels of this enzyme results in atrophy of epithelium and lack of maturation. It is been reported that post cricoid carcinoma, esophageal carcinoma and oral carcinoma show an increased association with iron deficiency anemia. According to John P. Richie Jr et al, Iron deficiency may be a cause for oral cancer through the induction of oxidative stress by the production of free radicals and reactive oxygen species that potentially cause cellular injury. This can be one of the reasons for the increase in malignant transformation rate seen in OSMF.  Epithelial atrophy and lack of proper maturation of epithelium are two important histological changes observed in the oral mucosa of patients with iron deficiency state. These changes in the epithelium are attributed to the increased percolation of esters of areca nut, which are known to stimulate fibrogenesis. The lack of iron may also lead to derangement in the inflammatory- reparative response of the lamina propria resulting in defective healing response and scarification. ,
| Conclusion|| |
In this study, mean hemoglobin, serum iron, percentage transferrin saturation, and serum ferritin levels were decreased in the study group compared to the control group and this difference was statistically significant whereas, the mean TIBC level was significantly increased in the study group compared to the control group. Our findings show that, an iron deficiency state is established among patients with OSMF. These results emphasize the role of iron in the pathogenesis of fibrosis. So, further research is required to understand the role of iron in the disease progression and malignant transformation of OSMF. This can aid in early intervention and effective management of the disease.
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Conflicts of interest
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| References|| |
Sudarshan R, Annigeri RG, Vijayabala GS. Pathogenesis of oral submucous fibrosis: the past and current concepts. IJOMP 2012;3:27-36.
McGurk M, Craig GT. Oral submucous fibrosis: Two cases of malignant transformation in Asian immigrants to the United Kingdom. Br J Oral Maxillofac Surg 1984;22:56-64.
Hazarey VK, Erlewad DM. Oral submucous fibrosis: study of 1000 cases from central India. J Oral Pathol Med 2007;36:12-7.
Paymaster JC. Cancer of buccal mucosa − A clinical study of 650 cases in Indian patients. Cancer 1955;9:431-5.
Murti PR, Bhonsle RB, Pindborg JJ et al.
Malignant transformation rate in oral submucous fibrosis over a 17-year period. Community Dent Oral Epidemiol 1985;6:340-1.
Shah N, Sharma PP. Role of chewing and smoking habits in the etiology of oral submucous fibrosis (OSF): a case-control study. J Oral Pathol Med 1998;27:475-9.
Pillai R, Balaram P, Sankara K. Pathogenesis of oral submucous fibrosis. Cancer 1992;69:2011-7.
Khanna SS, Karjodkar FR. Circulating immune complexes and trace elements (Copper, Iron and Selenium) as markers in oral precancer and cancer: a randomized, controlled clinical trial. Head Face Med 2006;2:33.
Taneja L, Anjana B, Vaishali K. Hemoglobin levels in patients with oral sub mucous fibrosis. JIAOMR 2007;19:329-33.
Shah N, Kumar R, Singh MK. Hematological and histological studies in oral submucous fibrosis. JIDA 1993;64:383-8.
Luquman M, Prabhu DP, Vidhya M. The role of serum copper and iron in oral sub mucous fibrosis. JIAOMR 2004;16:30-2.
Thakur M, Guttikonda VR. Estimation of hemoglobin, serum iron, total iron-binding capacity and serum ferritin levels in oral submucous fibrosis: A clinicopathological study. J Oral Maxillofac Pathol 2017;21:30-5. doi: 10.4103/jomfp.JOMFP_131_15. PMID: 28479683; PMCID: PMC5406814.
] [Full text]
Utsunomiya H, Tilakaratne WM, Oshiro K et al.
Extracellular matrix remodeling in oral submucous fibrosis: its stage-specific modes revealed by immunohistochemistry and in situ hybridization. J Oral Pathol Med 2005;34:498-507.
Neville BW, Damm DD, Allen CM et al.
Oral and Maxillofacial pathology. 2nd edn. USA: WB Saunders Publication; 2002.
Cox SC, Walker DM. OSMF-A review. Aust Dent J 1996;41:294-99.
Paissat DK. Oral submucous fibrosis. Int J Oral Surg 1981;10:307-12.
Rajendran R. Oral submucous fibrosis: etiology, pathogenesis, and future researOral submucous fibrosis: etiology, pathogenesis, and future research.Oral submucous fibrosis: etiology, pathogenesis, and future research. Bull World Health Organ 1994;72:985-996.
Tadakamadla J, Kumar S, Mamatha GP. Evaluation of serum copper and iron levels among oral submucous fibrosis patients. Med Oral Patol Oral Cir Bucal 2011;16:e 870-3.
Rajendran R, Vasudevan DM, Vijayakumar T. Serum levels of iron and proteins in oral submucous fibrosis (OSMF). Ann Dent 1990;49:23-5, 45.
Challacombe SJ. Hematological abnormalities in oral lichen planus, Candidiasis, Leukoplakia and nonspecific stomatitis. Int J Oral Maxillofac Surg 1986;15:72-80.
Shanmugham A, Water and Mineral Metabolism in Fundamentals of Biochemistry for Medical Students, 7th edn2006.p. 669-73.
Tadakamadla J, Kumar S, Mamatha GP. Evaluation of serum copper and iron levels among oral submucous fibrosis patients. Med Oral Patol Oral Cir Bucal 2011;16:e870-3.
Karthik H, Nair P, Gharote HP, Agarwal K, Bhat GR, Rajaram DK. Role of hemoglobin and serum iron in oral submucous fibrosis: a clinical study. Sci World J 2012;2012:254013.
Ranganathan K, Uma Devi M, Joshua E, Kirankumar K, Saraswathi TR. Oral submucous fibrosis A case control study in Chennai, South India. J Oral Pathol Med 2004;33:274-7.
Joshi SG. Submucous fibrosis of the palate and
pillars. Indian J Otolaryngyol 1953;4:1-4.
Pindborg JJ, Mehta FS, Gupta PC, Daftary DK. Prevalence of oral submucous fibrosis among 50, 915 Indian villagers. Br J Cancer 1968;22:646-654.
Kiran KK, Saraswathi TR, Ranganathan K, Devi MU, Elizabeth J. Oral submucous fibrosis: a clinico-histopathological study in Chennai. Indian J Dent Res 2007;18:106-11.
Anuradha CD, Devi CS. Serum protein, ascorbic acid & iron & tissue collagen in oral submucous fibrosis − a preliminary study. Indian J Med Res 1993;98:147-51.
Hall JE, Red Blood Cells, Anemia, and Polycythemia, In: Guyton and Hall The Text Book of Medical Physiology, 12th edn. Saunders: Elsevier. 2010 pp.413-422.
Fish DI. Hematinic investigations. In: Burnett D, Cocker J. The science of Laboratory diagnosis. 1st edn. UK: Isis Medical Media Ltd 1999 p. 337-340
Prime SS, MacDonald DG, Rennie JS. The effect of iron deficiency on experimental oral carcinogenesis in the rat. Br J Cancer 1983;47:413-8.
Richie JP Jr., Kleinman W, Marina P, Abraham P, Wynder EL, Muscat JE. Blood iron, glutathione, and micronutrient levels and the risk of oral cancer. Nutr Cancer 2008;60:474-82.
Murti PR, Bhonsle RB, Gupta PC, Daftary DK, Pindborg JJ, Mehta FS. Etiology of oral submucous fibrosis with special reference to the role of areca nut chewing. J Oral Pathol Med 1995;24:145-52.
Ahmad MS, Ali SA, Ali AS, Chaubey KK. Epidemiological and etiological study of oral submucous fibrosis among gutkha chewers of Patna, Bihar, India. J Indian Soc Pedod Prev Den 2006;24:84-9.
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