Objective: To estimate and compare the levels of serum copper and iron among subjects with oral submucous fibrosis (OSMF) of different clinical stages and healthy controls. Study Design: Study sample comprised of 50 patients clinically diagnosed with OSMF and 50 healthy controls who were matched for age and gender. OSMF patients were categorised by clinical staging. Serum estimation of copper and iron was done using atomic absorbtion spectrophotometry. Results: Mean copper and iron level differed significantly (p<0.000) between the patients and controls with patients exhibiting higher copper (134.1±20.16) and lower iron (114.78±23.47) levels in contrast to controls who presented lower copper (114.8±12.36) and higher iron (130.86±31.01) levels in serum. There was a definite trend as (P<0.0001) with cases having the lesion in faucial bands (1st stage) exhibiting the lowest serum copper and those in stage 3 (faucial, labial and buccal bands) presenting the highest copper levels in serum. Conclusions: Copper level increased and iron level decreased in study group in comparison to healthy controls. Copper level increased as clinical stage of oral submucous fibrosis increased. © Medicina Oral S. L

Kumar, Santhosh

Mamatha, G.P.

Tadakamadla, Jyothi

Repositori d'Objectes Digitals per a l'Ensenyament la Recerca i la Cultura

Med Oral Patol Oral Cir Bucal. 2011 Nov 1;16 (7):e870-3.                                                                                                                                       Serum copper and iron in oral submucous fibrosise870Journal section: Oral Medicine and PathologyPublication Types: ResearchEvaluation of serum copper and iron levels among oralsubmucous fibrosis patientsJyothi Tadakamadla 1, Santhosh Kumar 2, Mamatha GP 3 1 MDS Department of oral medicine and radiology, Vishnu Dental College, Bhimavaram, Andhra pradesh, 534202 India 2 MDS Department of preventive and community dentistry, Vishnu Dental College, Bhimavaram, Andhra pradesh, 534202 India 3 MDS Department of oral medicine and radiology, College of Dental Sciences, Davangere, Karnataka, 577004 India Department of oral medicine and radiology, Darshan Dental College and Hospital,  Udaipur,Rajasthan, 577004 India Correspondence:Department of oral medicine and radiology,Vishnu Dental College,Bhimavaram, Andhra pradesh, India. 534202docjyotia@yahoo.co.inReceived: 30/04/2010Accepted: 14/11/2010AbstractObjective: To estimate and compare the levels of serum copper and iron among subjects with oral submucous fibrosis (OSMF) of different clinical stages and healthy controls.Study Design: Study sample comprised of 50 patients clinically diagnosed with OSMF and 50 healthy controls who were matched for age and gender. OSMF patients were categorised by clinical staging. Serum estimation of copper and iron was done using atomic absorbtion spectrophotometry. Results: Mean copper and iron level differed significantly (p<0.000) between the patients and controls with pa-tients exhibiting higher copper (134.1±20.16) and lower iron (114.78±23.47) levels in contrast to controls who presented lower copper (114.8±12.36) and higher iron (130.86±31.01) levels in serum. There was a definite trend as (P<0.0001)  with cases having the lesion in faucial bands (1st stage) exhibiting the lowest serum copper and those in stage 3 (faucial, labial and buccal bands) presenting the highest copper levels in serum.Conclusions: Copper level increased and iron level decreased in study group in comparison to healthy controls. Copper level increased as clinical stage of oral submucous fibrosis increased. Key words: Oral submucous fibrosis, serum iron, serum copper, clinical staging.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 Nov 1;16 (7):e870-3.    http://www.medicinaoral.com/medoralfree01/v16i7/medoralv16i7p870.pdfArticle Number: 17083          http://www.medicinaoral.com/© Medicina Oral S. L. C.I.F. B 96689336 - pISSN 1698-4447 - eISSN: 1698-6946eMail:  medicina@medicinaoral.com Indexed in: Science Citation Index ExpandedJournal Citation ReportsIndex Medicus, MEDLINE, PubMedScopus, Embase and Emcare Indice Médico Españoldoi:10.4317/medoral.17083http://dx.doi.org/doi:10.4317/medoral.17083Med Oral Patol Oral Cir Bucal. 2011 Nov 1;16 (7):e870-3.                                                                                                                                       Serum copper and iron in oral submucous fibrosise871IntroductionOral submucous fibrosis (OSMF) is a chronic disease of the oral cavity, which is characterized by an epithelial and subepithelial inflammatory reaction followed by fi-broelastic changes in the submucosa. (1)The disease is most commonly seen in people of south Asian countries or in south Asian immigrants to other parts of the world. (2) Clinically, patients suffer from gradual, progressive alterations in oral mucosa resulting in compromised mouth opening to various degrees. (3)It is now evident that there exists a dose dependent rela-tionship between oral submucous fibrosis and both fre-quency and duration of chewing areca nut (4) which is a common habit in south and southeast Asia. (5)Presently, it is a well recognized, potentially premalig-nant condition with malignant potential and therefore a cause of concern for oral health care professionals. Ma-lignant transformation rates as high as 7.6% have been reported from the Indian subcontinent over a 17 year period. (6) In the search for possible causes of malig-nancies on the one hand, and the need for a modality affording early diagnosis and follow up on the other, at-tention was paid to the role played by trace elements in malignancies. (7)Among many trace elements, copper and iron are re-quired for the functioning of numerous enzymes and therefore it is reasonable to assume that variation in se-rum level of these biochemical markers may be associ-ated with the pathogenesis of oral cancer and precancer-ous states. (8) Iron has been recognized as an important element for maturation of epithelium and it is well documented that iron deficiency is associated with epithelial abnormali-ties in addition to malignancies like post cricoid carci-noma and tumours of the pharynx and mouth. (9)Thus biochemical alterations of copper and iron con-centrations in the serum of pre malignant patients can help not only in the early diagnosis, appropriate treat-ment but also as an indicator for prognosis.It has been postulated that altered serum copper and iron levels are observed among OSMF patients. Thus the present study aimed to estimate and compare the levels of serum copper and iron among subjects with oral submucuous fibrosis of different clinical stages and healthy controls.Material and Methods Study sample comprised of 50 patients clinically diag-nosed with OSMF and 50 healthy controls who were matched for age and gender. Patients attending the out-patient department of Darshan Dental College and Hos-pital, Udaipur were recruited in the study.Ethical clearance was taken from the Ethical Commit-tee, Darshan Dental College and Hospital and written informed consent was obtained from all the subjects.Subjects suffering from chronic systemic illness and those consuming areca nut (in control group) were ex-cluded. Inclusion criteria comprised subjects diagnosed with OSMF (in the study group) and subjects willing to provide written consent.  The staging of the OSMF was done according to the criteria of clinical grading by Haider SM et al. Clinical staging was done depending on topography and extent of distribution of bands. Stage 1 subjects had faucial bands while those in stage 2 presented faucial and buc-cal bands and among individuals in stage 3, faucial, buccal and labial bands were involved. (10)Ten ml of blood was drawn intravenously and was centrifuged at 1000 – 1500 RPM for 15 minutes. Sub-sequently, 5 ml of serum was collected which was analyzed for copper and iron with atomic absorbtion spectrophotometry in addition to haematological evalu-ation. Haemoglobin was assessed by Sahli’s method and erythrocytic sedimentation rate (ESR) was calculated by Westergren’s method.Data was entered in Microsoft Excel and analyzed us-ing Statistical Package for Social Sciences (SPSS 15.0, Chicago., IL). Means and standard deviations were cal-culated for serum copper and iron levels in study and control subjects.Independent samples ‘t’ test was used to compare the mean values of serum iron and copper between the study subjects and control group while one way analy-sis of variance (ANOVA) was used to assess the signifi-cance in difference between the mean copper and iron levels based on the staging of OSMF. Step wise linear regression analysis was executed to as-sess the influence of various independent variables (age, gender, hemoglobin, ESR, serum copper and iron lev-els) on the dependent variable (study or control group)  ResultsIn the present study, the youngest patient was 18 years of age while the oldest being 60 years. Among 50 pa-tients in both the study and control groups, 45 (90%) were males and 5 (10%) were females. It is evident from (Table 1) that mean copper and iron level differed sig-nificantly (p<0.05) between the patients and controls with patients exhibiting higher copper (134.1±20.16) and lower iron (114.78±23.47) levels in contrast to controls who presented lower copper (114.8±12.36) and higher iron (130.86±31.01) levels in serum.One way ANOVA revealed a statistically significant difference in mean serum copper levels among patients in various clinical stages of OSMF. There was a definite trend as (P<0.0001) shown in (Table 2) with cases hav-ing the lesion in faucial bands (1st stage) exhibiting the lowest serum copper and those in stage 3 (faucial, labial and buccal bands) presenting the highest copper levels Med Oral Patol Oral Cir Bucal. 2011 Nov 1;16 (7):e870-3.                                                                                                                                       Serum copper and iron in oral submucous fibrosise872in serum. However, there was decrease in serum iron concentration as clinical stage increased but the differ-ence observed was not statistically insignificant.Step wise multiple linear regression analysis was exe-cuted to assess the influence of age, gender, hemoglobin, ESR, serum copper and iron levels in predicting cases and controls. It is apparent from (Table 3) that serum copper and hemoglobin levels were the only significant variables. The first best predictor was serum copper level which exerted an influence of 25.3% whereas se-rum copper and hemoglobin levels together exerted an influence of 41.9%.    Discussion  Among many trace elements associated with OSMF, role of copper and iron have been extensively studied and have been the subject of a multitude of investiga-tions. In the present study, functional grading was not consid-ered for staging of OSMF as it is based on the degree of mouth opening which is also dependent on many other factors like cheek flexibility, pain during opening, ul-cers, vesicles, burning sensation and also psychological factors. It was observed that mean serum copper level was sig-nificantly high in study group than in control group. In accordance with our findings, many past studies have observed raised copper level in the sera of patients with oral premalignant and malignant lesions. (8,11)However, Trivedy et al. (12) observed that serum cop-per remained normal in OSMF patients in contrast to the present study; this difference could be attributed to the small sample size and absence of a control group in their study. Though the definite reason for increase in serum cop-per in premalignancies and malignancies is not known, it might be due to increased production of copper-con-taining ceruloplasmin by liver as an inflammatory re-sponse or due to decrease in catabolism of the serum ceruloplasmin. (13) It was noticed that all the subjects in the study group had the history of using areca nut and high levels of cop-per in areca nut plays an initiating role in stimulation of fibrogenesis. (14)Furthermore, a definite trend was observed with gradu-al increase in serum copper level as the clinical stage of OSMF increased. Thus, there could be a direct relation between serum copper and extent of fibrosis.Mean serum iron concentration in study subjects was lower than the control group. Anuradha and Devi have suggested that decreased iron levels in oral submucous fibrosis patients might be due to utilization of iron in collagen synthesis. (15)Furthermore, lack of iron in the tissues results in de-creased vascularity which facilitates percolation of  Group Mean Standard Deviation SignificanceCopper  Study 134.10 20.16 0.005 Control 114.84 12.36  Iron  Study 114.78 23.47        0.019 Control 130.86 31.01 Table 1. Mean serum copper and iron concentrations (µg/100 ml) in study group and control group .Independent samples‘t’ test.  Clinical staging n Mean Standard DeviationCopper* Stage 1 10 110.37 14.22 Stage 2 32 134.81 14.23 Stage 3 8 160.95 7.66 Total 50 134.10 20.16 IronStage 1 10 119.58 16.18 Stage 2 32 115.40 24.66 Stage 3 8 106.27 26.65 Total 50 114.78 23.47 Table 2. Copper and iron concentration (µg/100 ml) in serum of OSMF patients in relation to clinical staging. One way ANOVA. *p < 0.0001.Model R RSquareAdjustedR Square Std. Error of Estimate 120.503a0.647b0.2530.4190.245               0.437 0.406               0.387 Table 3. Step wise multiple linear regression analysis with age, gender, hemoglobin, ESR, serum Copper and Iron levels as independent variables and groups (patients and controls) as dependent variable. a Predictors: (Constant), Serum Copper level.    b Predictors: (Constant), Serum Copper level, Haemoglobin level.Med Oral Patol Oral Cir Bucal. 2011 Nov 1;16 (7):e870-3.                                                                                                                                       Serum copper and iron in oral submucous fibrosise873arecoline. In vitro studies on human fibroblasts ob-served that arecoline causes increased fibroblastic pro-liferation and collagen formation which is a hallmark of OSMF. (4)Nevertheless, the study is not free of limitations. The findings of the present study could not be generalized to all the OSMF patients because of the regional and cultural variation that occurs within and between the countries. The potential strong points of the study are that, equal number of cases and controls were included following stringent inclusion and exclusion criteria where subjects using areca nut were excluded from controls. Besides, Atomic Absorption spectro photometry was used to an-alyze the elements which is more accurate in elemental analysis than traditional calorimetry method. Further-more, in the present study the serum copper and iron levels were observed in relation to clinical staging. It can be concluded from the present study that serum copper and iron levels could be used as a potential prog-nostic and diagnostic markers in OSMF patients. How-ever, as there are controversial reports on the associa-tion of OSMF and these trace elements future studies are anticipated on a larger heterogeneous population to confirm the hypothesis.References 1. Mehrotra R, Pandya S, Chaudhary AK, Singh HP, Jaiswal RK, Singh M, et al. Lipid profile in oral submucous fibrosis. Lipids Health Dis. 2009;8:29. 2. Shin YN, Liu CJ, Chang KW, Lee YJ, Liu HF. Association of CT-LA-4 gene polymorphism with oral submucous fibrosis in Taiwan. J Oral Pathol Med. 2004;33:200-3. 3. Ceena DE, Bastian TS, Ashok L, Annigeri RG. Comparative study of clinicofunctional staging of oral submucous fibrosis with qualita-tive analysis of collagen fibers under polarizing microscopy. Indian J Dent Res. 2009;20:271-6. 4. Tilakaratne WM, Klinikowski MF, Saku T, Peters TJ, Warnaku-lasuriya S. Oral submucous fibrosis: review on aetiology and patho-genesis. Oral Oncol. 2006;42:561-8. 5. Zhang X, Li C, Liao Q, Reichart PA. Areca chewing in Xiangtan, Hunan province, China: interviews with chewers. J Oral Pathol Med. 2008;37:423-9. 6. Kiran Kumar K, Saraswathi TR, Ranganathan K, Uma Devi M, Elizabeth J. Oral submucous fibrosis: a clinico-histopathological study in Chennai. Indian J Dent Res. 2007;18:106-11. 7. Margalioth EJ, Schenker JG, Chevion M. Copper and zinc levels in normal and malignant tissues. Cancer. 1983;52:868-72. 8. Khanna SS, Karjodkar FR. Circulating immune complexes and trace elements (Copper, Iron and Selenium) as markers in oral pre-cancer and cancer : a randomised, controlled clinical trial. Head Face Med. 2006;2:33. 9. Prime SS, MacDonald DG, Rennie JS. The effect of iron defi-ciency on experimental oral carcinogenesis in the rat. Br J Cancer. 1983;47:413-8. 10. Haider SM, Merchant AT, Fikree FF, Rahbar MH. Clinical and functional staging  of oral submucous fibrosis. Br J Oral Maxillofac Surg. 2000;38:12-5. 11. Jayadeep A, Raveendran Pillai K, Kannan S, Nalinakumari KR, Mathew B, Krishnan Nair M, et al. Serum levels of copper, zinc, iron and ceruplasmin in oral leukoplakia and squamous cell carcinoma. J Exp Clin Cancer Res. 1997;16:295-300. 12. Trivedy CR, Warnakulasuriya KA, Peters TJ, Senkus R, Hazarey VK, Johnson NW. Raised tissue copper levels in oral submucous fi-brosis. J Oral Pathol Med. 2000;29:241-8. 13. Coates RJ, Weiss NS, Daling JR, Rettmer RL, Warnick GR. Cancer risk in relation to serum copper levels. Cancer Res. 1989;49:4353-6. 14. Trivedy C, Baldwin D, Warnakulasuriya S, Johnson N, Peters T. Copper content in Areca catechu (betel nut) products and oral sub-mucous fibrosis. Lancet. 1997;349:1447. 15. Anuradha CD, Devi CS. Serum protein, ascorbic acid & iron & tissue collagen in oral submucous fibrosis--a preliminary study. In-dian J Med Res. 1993;98:147-51.  References with links to Crossref - DOI    

Evaluation of serum copper and iron levels among oral submucous fibrosis patients

Objective: To estimate and compare the levels of serum copper and iron among subjects with oral submucous
fibrosis (OSMF) of different clinical stages and healthy controls.
Study Design: Study sample comprised of 50 patients clinically diagnosed with OSMF and 50 healthy controls
who were matched for age and gender. OSMF patients were categorised by clinical staging. Serum estimation of
copper and iron was done using atomic absorbtion spectrophotometry.
Results: Mean copper and iron level differed significantly (p<0.000) between the patients and controls with patients
exhibiting higher copper (134.1±20.16) and lower iron (114.78±23.47) levels in contrast to controls who
presented lower copper (114.8±12.36) and higher iron (130.86±31.01) levels in serum. There was a definite trend as
(P<0.0001) with cases having the lesion in faucial bands (1st stage) exhibiting the lowest serum copper and those
in stage 3 (faucial, labial and buccal bands) presenting the highest copper levels in serum.
Conclusions: Copper level increased and iron level decreased in study group in comparison to healthy controls.
Copper level increased as clinical stage of oral submucous fibrosis increased.No Full Tex

Mamatha, GP

Griffith Research Online

Medicina Oral Patología Oral y Cirugia Bucal

Objective: To estimate and compare the levels of serum copper and iron among subjects with oral submucous
fibrosis (OSMF) of different clinical stages and healthy controls.
Study Design: Study sample comprised of 50 patients clinically diagnosed with OSMF and 50 healthy controls
who were matched for age and gender. OSMF patients were categorised by clinical staging. Serum estimation of
copper and iron was done using atomic absorbtion spectrophotometry.
Results: Mean copper and iron level differed significantly (p<0.000) between the patients and controls with patients
exhibiting higher copper (134.1±20.16) and lower iron (114.78±23.47) levels in contrast to controls who
presented lower copper (114.8±12.36) and higher iron (130.86±31.01) levels in serum. There was a definite trend as
(P<0.0001) with cases having the lesion in faucial bands (1st stage) exhibiting the lowest serum copper and those
in stage 3 (faucial, labial and buccal bands) presenting the highest copper levels in serum.
Conclusions: Copper level increased and iron level decreased in study group in comparison to healthy controls.
Copper level increased as clinical stage of oral submucous fibrosis increased.No Full Tex

Evaluation of serum copper and iron levels among oral submucous fibrosis patients

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