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Investigating the relationship between Vitamin D and Bone Mineral Density among Coeliac patients attending Ibn Sina Hospital

Malaz Omer Basheer1, MBBS, MD; Fathia Mubarak Khojali2, B.S, MSC; Omer Osman Kheir3, BDS, MPTH, MD, PG RM & Bio; Sagangal Abdelhadi Mohammed2, MBBS, MD; Hala Ibrahim Abu Al-hassan Abdalla2, MBBS, MD

1 Department of Hepatology, Ibn Sina Hospital- Khartoum-Sudan;
2 Department of Coeliac, Ibn Sina Hospital. Khartoum- Sudan;
3 Department of Research, National center of Gastrointestinal and Liver disease, Khartoum, Sudan.

Conflict-of-interest statement: The authors declare that there is no conflict of interest regarding the publication of this paper.

Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http: //creativecommons.org/licenses/by-nc/4.0/

Correspondence to: Omer Osman Kheir, Department of Research, National center of Gastrointestinal and Liver disease, Khartoum, Sudan.
Email: omerokheir@gmail.com
Telephone: +249999608091

Received: February 10, 2020
Revised: May 10, 2020
Accepted: April 16, 2020
Published online: June 21, 2020

ABSTRACT

Aim: To investigate the correlation between vitamin D and bone mineral density among coeliac patients.

Material and Methods: This is a cross sectional hospital-based study carried out in Ibn-Sina hospital from July - November 2019. Forty-two participants with coeliac disease were recruited in this study aged 18 years or above who attended the coeliac clinic. Data was collected using well-constructed questionnaires. Their laboratory investigations along with serum 25(OH)D levels were done. Bone mineral density was measured using Furuno’s CM-200 light ultrasound bone densitometer. Data was analyzed by using Statistical Packages for Social Sciences (SPSS) software.

Results: A total of 42 participants were enrolled. Eighty one percent of the sample were female and 19% were male. The mean age of our sample was 27.3095 ± 9.47780SD. This study demonstrated a moderate positive relationship between vitamin D level and T- score level with (r = 0.437), and statistically significant (p < 0.004). There was a significant relation between T -score and adherence to gluten free diet (p < 0.012). All the participants stated no previous history of bone fracture. Moreover, the results revealed no coeliac patients with osteoporosis.

Conclusion: There was correlation between vitamin D and BMD. Our results suggest, there is an underlying factor related to bone fracture among patients with coeliac disease. Furthermore, we suggest that serum calcium investigation is not predictive of low BMD in coeliac patients.

Key words: Coeliac; Vitamin D; Bone Mineral Density

© 2020 The Authors. Published by ACT Publishing Group Ltd. All rights reserved.

Basheer MO, Khojali FM, Kheir OO, Mohammed SA, Abdalla HIA. Investigating the relationship between Vitamin D and Bone Mineral Density among Coeliac patients attending Ibn Sina Hospital. Journal of Gastroenterology and Hepatology Research 2020; 9(3): 3191-3195 Available from: URL: http://www.ghrnet.org/index.php/joghr/article/view/2800

INTRODUCTION

Coeliac disease (CD) is one of the most prevalent malabsorptive syndromes, of either one or more nutrients. It was initially thought to be a disease of Caucasians, until realizing it was also common in non-Caucasians and other parts of the world, including Asian and African countries[1,2].

CD is a highly frequent disease[3] that affects around 1% of the world population according to serology-based screening studies[4].

When CD is diagnosed through the childhood period it estimated during this period, one-third of affected children have osteoporosis, one-third have osteopenia and only the remaining third recall a normal bone mineral density (BMD)[5].

In fact, coeliac patients without gastrointestinal symptoms may have low BMD, which increases after start of the gluten free diet (GFD)[6].

Untreated adult coeliac patients have shown a 45 % decline in calcium absorption followed by an improvement of 52 % after 6 months of gluten free diet(GFD) adherence[7]. Previous Spanish study reveal that vitamin D, at the time of diagnosis, less than 5 % of Spanish adult CD patients had normal serum levels[8].

Vitamin D deficiency is common among patients with CD, although there are no changes in the expression of vitamin D receptors[9] or a greater number of receptor gene mutations interfering with the metabolism of this vitamin[10] in this population.

Several authors have suggested that deficits in other fat-soluble vitamins (A, K and E) and even water-soluble vitamins (C, B12, folic acid and B6) or minerals (such as iron, calcium, phosphorus, copper, zinc, boron, fluorine), which are all required for normal bone metabolism[8,11], also consequence from the intestinal malabsorption displayed by coeliac patients.

In any case, once the glutenfree diet (GFD) is instituted, most coeliac children catch up to their height-weight growth curve and accelerate their rate of bone mineralization, so that most achieve normal peak bone mass by the time bone growth is completed. The main problem arises when CD is diagnosed during adulthood, once bone growth is complete and peak bone mass has been reached. Among these patients, the prevalence of osteoporosis is at least twice that of the unaffected population in the same age range[12,13]. There is scarce information about the vitamin d and BMD among coeliac patients in Sudan. Therefore, the purpose of this study was to examine the correlation between vitamin D and BMD among patients with coeliac disease.

METHODS

This is a cross sectional hospital-based study carried out in Ibn-Sina hospital from July - November 2019.This Hospital is a tertiary referral hospital concentrated on 3 specialties: Gastroenterology (GI), Nephrology-Urology, and Ear, Nose, Throat. The institution of the GI unit at Ibn-Sina Hospital was a fundamental in the development of gastroenterology services in Sudan[14]. A study protocol was submitted to the ethics committee of the Sudanese Medical Specialization Board (S.M.S.B) and Ibn-Sina hospital for approval, ensuring adherence to ethical principles such as those specified by the World Medical Association Declaration of Helsinki, and ethical approval was granted. Following an explanation of the study, each participant signed an informed consent form. The participants were assured anonymity and confidentiality and that declining to participate would not affect their current and future treatment.

Forty-two participants with coeliac disease were recruited in this study aged 18 years or above who attended the coeliac clinic. Patients on steroids, or with other diseases affecting the bone or refused to participate in this study were excluded from the study. The sample size was calculated using epi info software (www.cdc.gov/epiinfo). Convenience nonprobability sampling method was used for recruitment.

Data was collected using well-constructed questionnaires. These questionnaires were filled by trained medical doctors. The questionnaire includes the following variables age, gender, residence, level of education, employment, adherence to gluten free diet, previous history of pathological fracture, body mass index (BMI), vitamin D level, Bone mineral density and serum calcium.

The BMI was calculated as weight/height2 (kg/m2). Based on WHO criteria[15]. Bone mineral density was measured using Furuno’s CM-200 light ultrasound bone densitometer (Furuno electric Co.LTD, Japan)[16].T-score criteria which is similar to WHO’s[17] criteria T- score is divided into three groups : Normal is a T-score of -1.0 or higher, Osteopenia is defined as between -1.0 and -2.5 and Osteoporosis is defined as -2.5 or low Vitamin D deficiency is categorized as a serum 25-hydroxyvitamin D level of less than 20 ng per mL (50 nmol per L), and insufficiency is categorized as a serum 25-hydroxyvitamin D level of 20 to 30 ng per mL (50 to 75 nmol per L)[18].

Data was entered, coded, and cleaned in excel master sheet. Data was analyzed by using Statistical Packages for Social Sciences (SPSS) 23.0 software. Shapiro-Wallis test was used to assess the normality. Tests used for analysis spearman’s for correlation test, Mann Whitney u test, Kruskil-Wallis test and Dunnett’s teste for pairwise comparison, as appropriate. p < 0.05 is considered statistically significant (Confidence Interval: CI 95%).

RESULTS

A total of 42 participants were enrolled by a response rate of 85.7%. all sample were collected after excluding patients did not meet the eligible criteria or refuse to participate among which 81% of the sample were female and 19% were male. Ninety percent of participants live in urban area and 78% of them with university education or higher education (Table 1). Regarding the occupation 47, 6% of the sample was unemployed, 23.8% of the individuals are housewife and 28.6% were employed showed in table[1]. Twenty-eight participants stated that the diseases started less than 5 years, while 7 individuals stated that diseases started between 5-10 years and the last group stated they had the disease for more than 10 years. Regarding the adherence to gluten free diet 45.2% were good adherence, 45.2% were average adherence and 9,5% were bad adherence. The sample distribution according t-score 42.9% were osteopenia, while 57.1% were normal bone density. (Table 1). All participants stated that no previous history of bone fracture (100%) (Table1).

The mean age of our sample was 27.3095 ± 9.47780SD, BMI mean was 19.7588 ± 4.40561 SD, vitamin D level mean was 31.7531 ± 14.47192 SD, T- score mean was -0.9779 ± 0.64518 SD and the mean for serum ca++ 9.1791 ± 0.65584SD (Table 2).

This study demonstrated a moderate positive relationship between vitamin D level and T- score level with (r = 0.437), and statistically significant (p < 0.004) displayed in (table 3). So was the vitamin d and body mass index (BMI), also showed a moderate positive relationship with (r = 0.328), and statistically significant (p < 0.034) (Table 3).

There was no correlation between vitamin D level and age r = -0.46 and statistically not significant (p > 0.773) (Table 3). Also, there was no correlation between vitamin D and serum calcium (r = -0.06) and statistically not significant (p > 0.704).

This study negative a moderate correlation between T-score level and age(r = -0.356), and statistically significant (p < 0.021) (Table 4).

There was no correlation between t-score and the BMI r = -0.109 and statistically not significant (p > 0.493) (table4). Furthermore, the was no correlation between t-score and serum calcium (r = 0.007), and statistically not significant (p > 0.962).

According to Mann-Whitney U there was no significant relationship between the vitamin D and the gender (p > 0.785), so was vitamin D and occupation, also statistically not significant (p > 0.302) (Table 5). Kruskal Wallis test showed there was no significant relationship between vitamin D level and level of education (p > 0.148), moreover, There was no significant relationship between vitamin D and adherence to gluten free diet with (p > 0.81) (Table 5). so was the t-score and duration of coeliac disease, also statistically not significant (p > 0.400) (Table 5).

However, there was a significant relation between t -score and adherence to gluten free diet (p < 0.012). pairwise comparison test was performed and adjust it Bonferroni showed a significant between the good adherence to gluten free diet group and bad adherence to gluten free diet group (p < 0.32) (Table 6).

Table 1 Sociodemographic and exposure characteristics (n=42).
VariableSubgroupFrequencyPercentage
GenderMale819.00%
Female3481.00%
ResidenceRural49.50%
Urban3890.50%
Education levelnon educated12.40%
primary49.50%
Secondary49.50%
university and above3378.60%
Occupationunemployed2047.60%
housewife1023.80%
employee1228.60%
Adherence to Gluten free dietgood1945.20%
average1945.20%
bad49.60%
Duration of Coeliac diseaseless than 5 years2866.60%
5- 10 years716.70%
more than 10 years716.70%
previous history of bone fractureyes00%
no42100

Table 2 Age, BMI, Vitamin D level, T-score and serum calcium (in means ± SD).
  NMeanStd. Deviation
AGE4227.30959.4778
Body Mass Index4219.75884.40561
Vitamin D Level4231.753114.47192
T-Score42-0.97790.64518
Serum calcium429.17910.65584

Table 3 Correlation coefficients and P-value between Vitamin D , T- score , age, serum calcium and BMI.
  Correlation CoefficientP-value
Vitamin D Level /T-Score0.437* <0.004
Vitamin D Level / Serum Calcium-0.06 >0.704
Vitamin D level/ Age-0.046 >0.773
Vitamin D/ Body Mass Index0.328* <0.034

Table 4 Correlation coefficients and P-value between T- score, age, serum calcium and BMI.
  Correlation CoefficientP-value
Age /T- score-.356* <0 .021
Serum Calcium/T-score0.007 >0.962
Body Mass Index/t-score-0.109 >0.493

Table 5 Analysis of Characteristics according to vitamin d level:(n=42).
VariableSubgroupFrequencyMean rankP-value
GenderMale822.56>.785
Female3421.25
ResidenceRural420>0.797
Urban3821.66
Education levelnon educated17>0.148
primary417.75
Secondary433
university and above3321
Occupationunemployed2021.33>0.966
housewife1020.95
employee1222.25
Adherence to Gluten free dietgood1925.68>0.81
average1919.21
bad412.5
Duration of Coeliac diseaseless than 5 years2819.54>0.267
5- 10 years727.71
more than 10 years723.14
A-P-value (P<0.05) results from Mann-Whitney and Kruskal-Wallis tests for the differences between subgroups

Table 6 Analysis of Characteristics according to T- score:(n=42).
VariableSubgroupFrequencyMean rankP-value
GenderMale821.5 >0.100
Female3421.5
ResidenceRural423.38>0.748
Urban3821.3
Education levelnon educated11>0.403
primary420.75
Secondary422.88
university and above3322.05
Occupationunemployed2024.63>0.282
housewife1018
employee1219.21
Adherence to Gluten free dietgood1927.08<0.012
average1918.37
bad49.88
Duration of Coeliac diseaseless than 5 years2822.54>0.400
5- 10 years723.07
more than 10 years715.79
A-P-value (p < 0.05) results from Mann-Whitney and Kruskal-Wallis tests for the differences between subgroups

DISCUSSION

The study should be considered with its limitations. The sample was made up of participants attending the hospital with coeliac disease; a random sample population would have been more representative. However, the study design was made to obtain information on vitamin D and BMD on patients with coeliac disease.

Our study revealed that there is a significant correlation between vitamin D and Bone Mineral Density which agreed to previous studies conducted by Ardawi et al[19,20].

The prevalence of osteopenia and osteoporosis is lower in blacks as compared to that seen in the whites[21]. Our data showed that no participants had osteoporosis this may be due to our sample been taken from patients who are doing follow up in the hospital and they started counseling and following the gluten free diet. Also, our sample was small; if we took a larger sample and more diverse may include patients with osteoporosis.

Vitamin D deficiency is relatively uncommon in healthy young patients; the deficiency is common in elderly population, particularly individuals where sunlight is limited[22]. Also, vitamin D deficiency is common on patients with coeliac disease[9].

This study examined the relationship between vitamin D levels and age but there was no significant difference in the vitamin D levels of different age group. Most of our age sample includes young patients. Our result is supported by previous study carried out by Lbronicietal which had similar result[23].

The prevalence of vitamin D deficiency and insufficiency were high among CD patients. This is can be due to dietary vitamin D is absorbed as a fat-soluble vitamin in small intestine, and because of intestinal involvement in CD its absorption decreases thus leading to deficiency of particular vitamin D[24].

This study showed a negative moderate relationship between t-score and age. Previous study demonstrated a negative correlation between age and BMD namely, greater age was correlated with lower BMD, corroborating the work of Biana et al[25] who claimed that this mainly occurs at the end of the last decade of life, and may correspond to 5-10% of total bone mass/decade. The reasons for this may include nutritional deficiencies, some chronic diseases, and lack of exercise.

Vitamin D is also deficient among CD patients despite the fact that diet only provides 5-10% of required vitamin D[26,27].

Our study revealed that no significant relationship between t- score and BMI however, Previous studies concluded that when BMI increases, BMD levels will also increase[28,29], which disagree with our findings. The reason for this our sample was taken from patients with coeliac disease, therefore most of the patients with normal weight or underweight.

One study has evaluated vitamin D status in children living in Northern Italy and found out that almost half of the study population who were obese had vitamin D deficiency[30].

Our results discovered that there was a significant association between vitamin D level and BMI. A previous study showed that there was an inverse relationship between vitamin D and BMI[18,31,32].

Previous study stated that there was no significant change in fracture risk after diagnosis of coeliac disease. These results suggest that the concerns about fracture risk in patients with coeliac disease have been overstated[33]. Our study revealed that our entire sample had no previous history of bone fracture which supported by K Thomson et al[33].

One study has reported an increased risk of peripheral fractures in those with coeliac disease. However, most fractures were recorded prior to diagnosis or in those non-compliant with their gluten-free diet[34]. Our result revealed that there is no history of bone fracture among patients with coeliac disease including patients stated that didn’t adhere to GFD. These results suggest that there is may be underlying factor that may influence bone fracture among coeliac patients.

Jadwiga Szymczak et al. noticed that gluten-free diet improves calcium and vitamin D absorption, diminishes secondary hyperparathyroidism, and increases BMD, but does not guarantee full recovery[35].

Our study found that there is no significant relationship between vitamin d and adherence to gluten free diet.

However, there was significant relationship between t- score and adherence to free gluten diet. the significant different occur between poor adherence group and good adherence group where the bone density increase with good adherence to gluten free diet. These finding supported by previous study[36-39]. Regarding vitamin d and serum there was no significant relationship, there was no relationship between BMD and serum calcium, also statistically not significant. In Sudan measuring the serum calcium is routine investigation for those with coeliac disease. Our result suggested the serum calcium investigation is not necessary in routine investigation and may help to reduce the cost for coeliac patients.

Khartoum is classified as hot desert climate (hot, dry and sunny) with dry season occur in winter according to Köppen climate classification[40,41]. We suggest further study to examine the relationship between bone mineral density and life style, mode of transportation, physical activity, and sun exposure among coeliac patients.

Conclusion

There was a correlation between vitamin D and BMD. There were no pathological fractures or osteoporosis among diagnosed coeliac disease sample which suggest that is an underlying factor related to bone fracture. In this study, serum calcium level was not predictive of low BMD in coeliac patients.

REFERENCES

1. Makharia G, Verma A, Amarchand R, Bhatnagar S, Das P, Goswami A, Bhatia V, Ahuja V, Datta Gupta S, Anand K. Prevalence of celiac disease in the northern part of India: A community-based study. Journal of Gastroenterology and Hepatology. 2011; 26(5): 894-900. [PMID: 21182543]; [DOI: 10.1111/j.1440-1746.2010.06606.x]

2. Kang J, Kang A, Green A, Gwee K, Ho K. Systematic review: worldwide variation in the frequency of coeliac disease and changes over time. Alimentary Pharmacology & Therapeutics. 2013; 38(3): 226-245. [PMID: 23782240.]; [DOI: 10.1111/apt.12373]. Epub 2013 Jun 18

3. Rodrigo-Sáez L, Fuentes-Álvarez D, Álvarez-Mieres N, Niño-García P, de Francisco García R, Riestra-Menendez S. Enfermedad Celiaca en el 2009. RAPD Online 2009; 32: 339-57.

4. Reilly N, Green P. Epidemiology and clinical presentations of celiac disease. Semin Immunopathol. 2012; 34(4): 473-478. [PMID: 22526468.]; [DOI: 10.1007/s00281-012-0311-2. Epub 2012 Apr 24.

5. Goddard C, Gillett H. Complications of coeliac disease: are all patients at risk? Postgrad Med J. 2006; 82(973): 705-712. [PMID: 17099088]; [PMCID: PMC2660494]; [DOI: 10.1136/pgmj.2006.048876]

6. Mustalahti K, Collin P, Sievänen H, Salmi J, Mäki M. Osteopenia in patients with clinically silent coeliac disease warrants screening. The Lancet. 1999; 354(9180): 744-745. [PMID: 10475193]; [DOI: 10.1016/S0140-6736(99)01990-X]

7. Ciacci C, Cirillo M, Mellone M, Basile F, Mazzacca G, De Santo NG. Hypocalciuria in overt and subclinical celiac disease. Am J Gastroenterol 1995; 90: 1480e4. [PMID: 7661174]

8. García-Manzanares Á, Tenias J, Lucendo A. Bone mineral density directly correlates with duodenal Marsh stage in newly diagnosed adult celiac patients. Scand J Gastroenterol. 2012; 47(8-9): 927-936. [PMID: 22587226]; [DOI: 10.3109/00365521.2012.688217]

9. Colston K, Mackay A, Finlayson C, Wu J, Maxwell J. Localisation of vitamin D receptor in normal human duodenum and in patients with coeliac disease. Gut. 1994; 35(9): 1219-1225. [PMID: 7959227. PMC1375697]; [DOI: 10.1136/gut.35.9.1219]

10. H. Vogelsang, E. K. Suk, M. Janisiw, C. Stain, W. R. Mayr, S. Panzer. Calcaneal Ultrasound Attenuation and Vitamin-D-Receptor Genotypes in Celiac Disease. Scand J Gastroenterol. 2000; 35(2): 172-176. [PMID: 10720115.]; [DOI: 10.1080/003655200750024344]

11. Stazi A, Trecca A, Trinti B. Osteoporosis in celiac disease and in endocrine and reproductive disorders. World J Gastroenterol. 2008; 14(4): 498. [PMID: 18203279. PMC2681138]; [DOI: 10.3748/wjg.14.498]

12. Sundar N, Crimmins R, Swift G. Clinical presentation and incidence of complications in patients with coeliac disease diagnosed by relative screening. Postgrad Med J. 2007; 83(978): 273-276. [PMID: 17403956]; [PMC2600030]; [DOI: 10.1136/pgmj.2006.052977]

13. Younes M, Ben Youssef H, Safer L, Fadoua H, Zrour S, Bejia I, Touzi M, Najjar MF, Saffar H, Bergaoui N. Prevalence of bone loss in adult celiac disease and associated factors: a control case study. Tunis Med. 2012 Feb; 90(2): 129-35. [PMID: 22407624]

14. WGO Khartoum Training Center Inauguration and Gastro 2015! Journal of Clinical Gastroenterology. 2015; 49(7): i-ii. [PMID: 26164605]; [DOI: 10.1097/MCG.0000000000000371]

15. WHO.Obesity : preventing and managing the global epidemic: report of a WHO Consultation on Obesity, Geneva, 3-5 June 1997. World Health Organization. https://apps.who.int/iris/handle/10665/63854

16. Ultrasound Bone Densitometer CM-200 | Ultrasound Bone Densitometer | Products | FURUNO. Furuno.com. [Online] 2019. [Cited: August 20, 2019.

17. Kanis J, Kanis J. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: Synopsis of a WHO report. Osteoporosis Int. 1994; 4(6): 368-381. [PMID: 7696835]; [DOI: 10.1007/bf01622200]

18. Holick M. Vitamin D Deficiency. N Engl J Med. 2007; 357(3): 266-281. [PMID: 17634462]; [DOI: 10.1056/NEJMra070553]

19. Ardawi M, Qari M, Rouzi A, Maimani A, Raddadi R. Vitamin-D inadequacy in Saudi postmenopausal women with osteoporosis. Bone. 2010; 47: S192. [DOI: 10.1016/j.bone.2010.04.455]

20. Ardawi M, Sibiany A, Bakhsh T, Qari M, Maimani A. High prevalence of vitamin D deficiency among healthy Saudi Arabian men: relationship to bone mineral density, parathyroid hormone, bone turnover markers, and lifestyle factors. Osteoporosis International. 2012; 23(2): 675-686. [PMID: 21625888]; [DOI: 10.1007/s00198-011-1606-1]

21. Looker A, Orwoll E, Johnston C, Lindsay R, Wahner H, Dunn W Calvo MS, Harris TB, Heyse SP. Prevalence of Low Femoral Bone Density in Older U.S. Adults from NHANES III. Journal of Bone and Mineral Research. 1997; 12(11): 1761-1768. [PMID: 9383679]; [DOI: 10.1359/jbmr.1997.12.11.1761]

22. Bischoff-Ferrari H. The 25-hydroxyvitamin D threshold for better health. J Steroid Biochem Mol Biol. 2007; 103(3-5): 614-619. [PMID: 17227709]; [DOI: 10.1016/j.jsbmb.2006.12.016]

23. Labronici P, Blunck S, Lana F, Esteves B, Franco J, Fukuyama J, Pires RES. Vitamin D and its Relation to Bone Mineral Density in Postmenopause Women. Revista Brasileira de Ortopedia (English Edition). 2013; 48(3): 228-235. [PMID: 31214537]; [PMCID: PMC6565868]; [DOI: 10.1016/j.rboe.2012.07.003]

24. Kemppainen T, Kröger H, Janatuinen E, Arnala I, Kosma VM, Pikkarainen P, Julkunen R, Jurvelin J, Alhava E, Uusitupa M. Osteoporosis in adult patients with celiac disease. Bone. 1999; 24(3): 249-255. [PMID: 10071918]; [DOI: 10.1016/s8756-3282(98)00178-1]

25. Pluijm S, Visser M, Smit J, Popp-Snijders C, Roos J, Lips P. Determinants of Bone Mineral Density in Older Men and Women: Body Composition as Mediator. J Bone Miner Res. 2001; 16(11): 2142-2151. [PMID: 11697812]; [DOI: 10.1359/jbmr.2001.16.11.2142]

26. Jahnsen J, Falch J, Mowinckel P, Aadland E. Vitamin D Status, Parathyroid Hormone and Bone Mineral Density in Patients with Inflammatory Bowel Disease. Scand J Gastroenterol. 2002; 37(2): 192-199. [PMID: 11843057]; [DOI: 10.1080/003655202753416876]

27. Colston K, Mackay A, Finlayson C, Wu J, Maxwell J. Localisation of vitamin D receptor in normal human duodenum and in patients with coeliac disease. Gut. 1994; 35(9): 1219-1225. [PMID: 7959227]; [PMCID: PMC1375697]; [DOI: 10.1136/gut.35.9.1219]

28. Kirchengast, Sylvia, Bert Peterson, Gertrude Hauser and Wolfgang Knogler. “[Significance of body weight status for bone density in the elderly and very old].” Zeitschrift fur Gerontologie und Geriatrie 2001; 34(4): 313-8. [PMID: 11584716]; [DOI: 10.1007/s003910170055]

29. Doğan A, Nakipoğlu-Yüzer GF, Yıldızgören MT, Özgirgin N. Is age or the body mass index (BMI) more determinant of the bone mineral density (BMD) in geriatric women and men? Archives of Gerontology and Geriatrics. 2010; 51(3): 338-341. [PMID: 20202698]; [DOI: 10.1016/j.archger.2010.01.015]

30. Bellone S, Esposito S, Giglione E, Genoni G, Fiorito C, Petri A, Bona G, Prodam F. Vitamin D levels in a paediatric population of normal weight and obese subjects. J Endocrinol Investig. 2014; 37(9): 805-809. [PMID: 24923900]; [DOI: 10.1007/s40618-014-0108-3]

31. Rovner AJ, O’Brien KO. Hypovitaminosis D Among Healthy Children in the United States: a review of the current evidence. Arch Pediatr Adolesc Med 2008; 162(6): 513. [PMID: 18524740]; [DOI: 10.1001/archpedi.162.6.513]

32. Vierucci F, Del Pistoia M, Fanos M, Gori M, Carlone G, Erba P, Massimetti G, Federico G, Saggese G.Vitamin D status and predictors of hypovitaminosis D in Italian children and adolescents: a cross-sectional study. Eur J Pediatr. 2013; 172(12): 1607-1617. [PMID: 23959324]; [DOI: 10.1007/s00431-013-2119-z]

33. Thomason K, West J, Logan RF, Coupland C, Holmes GK. Fracture experience of patients with coeliac disease: a population-based survey. Gut. 2003; 52(4): 518-522. [PMID: 12631662]; [PMCID: PMC1773600]; [DOI: 10.1136/gut.52.4.518

34. Vazquez H, Mazure R, Gonzalez D, Flores D, Pedreira S, Niveloni S, Smecuol E, Mauriño E, Bai JC. Risk of fractures in celiac disease patients: a cross-sectional, case-control study. Am J Gastroenterol. 2000; 95(1): 183-189. [PMID: 10638580]; [DOI: 10.1111/j.1572-0241.2000.01682.x]

35. Szymczak J, Bohdanowicz-Pawlak A, Waszczuk E, Jakubowska J. Low bone mineral density in adult patients with coeliac disease. Endokrynologia Polska 2012; 63(4): 270-276. [PMID: 22933162

36. Turner J, Pellerin G, Mager D. Prevalence of Metabolic Bone Disease in Children With Celiac Disease Is Independent of Symptoms at Diagnosis. J Pediatr Gastroenterol Nutr. 2009; 49(5): 589-593. [PMID: 19644400]; [DOI: 10.1097/MPG.0b013e31819ca18e]

37. Kavak US, Yüce A, Koçak N, Demir H, Saltik İN, Gürakan F, Ozen H. Bone Mineral Density in Children With Untreated and Treated Celiac Disease. J Pediatr Gastroenterol. Nutr. 2003; 37(4): 434-436. [PMID: 14508213]; [DOI: 10.1097/00005176-200310000-00007]

38. Jatla M, Zemel BS, Bierly P, Verma R. Bone Mineral Content Deficits of the Spine and Whole Body in Children at Time of Diagnosis With Celiac Disease. J Pediatr Gastroenterol. Nutr 2009; 48(2): 175-180. [PMID: 19179879]; [DOI: 10.1097/MPG.0b013e318177e621]

39. Tau C, Mautalen C, De Rosa S, Roca A, Valenzuela X. Bone mineral density in children with celiac disease. Effect of a Gluten-free diet. Eur J Clin Nutr. 2005; 60(3): 358-363. [PMID: 16319837]; [DOI: 10.1038/sj.ejcn.1602323]

40. Geiger, R.: Ch. Klassifikation Der Klimate Nach W. Köppen, in: Landolt-Börnstein - Zahlenwerte Und Funktionen Aus Physik, Chemie,Astronomie, Geophysik Und Technik, vol. Band III, alte Serie, pp. 603-607, Springer, Berlin, 1954.

41. Geiger, R., Pohl, W. Revision of the Köppen-Geiger Klimakarte, der Erde (Justus-Perthes, Darmstadt, 1953). Eine neue Wandkarte der. Klimagebiete der Erde. Erdkunde, 8(1954): 58-61

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