Prevalence of Metabolic Bone Disease in Children With Celiac Disease Is Independent of Symptoms at Diagnosis : Journal of Pediatric Gastroenterology and Nutrition

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Original Articles: Gastroenterology

Prevalence of Metabolic Bone Disease in Children With Celiac Disease Is Independent of Symptoms at Diagnosis

Turner, Justine*; Pellerin, Genevieve; Mager, Diana†,‡

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Journal of Pediatric Gastroenterology and Nutrition: November 2009 - Volume 49 - Issue 5 - p 589-593
doi: 10.1097/MPG.0b013e31819ca18e
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Celiac disease is one of the most common malabsorptive disorders seen in children (2). This autoimmune gastrointestinal disorder occurs in genetically predisposed individuals after ingestion of gluten peptides found in wheat, barley, and rye (2). This disease affects mainly white individuals of northern European descent and approximately 1% of the North American population (2). One of the most common complications of celiac disease is metabolic bone disease, including osteomalacia, osteopenia, and osteoporosis (3).

Calcium, vitamin D, and vitamin K are important micronutrients for bone health and are commonly malabsorbed in untreated celiac disease (4). In addition to the role that malabsorption of these dietary factors plays in the etiology of the observed metabolic bone disease, other factors, such as sunlight exposure, may be relevant. It is probable that children with celiac disease living in climates above the 54th parallel, such as northern Alberta, are especially vulnerable to bone health complications, due to limitation in endogenous vitamin D production (5).

We are now aware that many individuals with celiac disease experience no gastrointestinal symptoms; however, a similar pattern of mucosal damage and malabsorption will occur as is observed in their symptomatic counterparts (6). The varying presentations of celiac disease are a special problem for bone health because many children and adolescents will live with undiagnosed or poorly treated celiac disease for many years. Such silent presentations of celiac disease may delay the diagnosis, which is often only determined given prolonged gastrointestinal symptoms.

Childhood and adolescence are crucial times for bone mineral accrual (7). In contrast to adults with celiac disease strict adherence to a gluten-free diet in childhood can lead to dramatic improvements in bone mineral density (BMD), even after 1 year (8). It has been postulated that persisting osteopenia and osteoporosis in adults with celiac disease, despite a gluten-free diet, reflects failure to reach peak bone mass during childhood onset, and potentially silent, disease (9). The objective of the present study is to determine the prevalence of metabolic bone disease in children diagnosed with celiac disease and living in northern Alberta. We hypothesize that decreased BMD in this population would be prevalent, regardless of symptoms at presentation.


A retrospective review of clinic charts (n = 74), of children (3.3–16.1 years) clinically diagnosed with celiac disease (April 30, 1989–June 15, 2008) in the Celiac Clinic at the Stollery Children's Hospital was conducted to assess the prevalence of metabolic bone disease and the variables contributing to bone health in this population. Eighty-three charts were excluded from review because of lack of available dual energy x-ray absorptiometry (DXA) scan results within an 18-month period from diagnosis. Twenty-three were excluded because the patients had alternate diagnosis, such as type 1 diabetes, hypothyroidism, or Down syndrome, which would affect bone density results independent of the diagnosis of celiac disease. A further 2 patients who declined diagnostic intestinal biopsy and 1 patient who resided outside northern Alberta were also excluded.

Primary outcome variables included lumbar BMD, BMD z score, and bone mineral content (BMC). Secondary outcome variables included presence of symptoms leading to the diagnosis of celiac disease or the absence of symptoms at diagnosis, bone age (radiological measurement), bone surface area, antitissue transglutaminase (aTTG), ferritin, serum vitamin D, height, weight, body mass index (BMI), height/weight z scores and corresponding percentiles. Confounding variables included ethnicity, medical and family history, and calcium and vitamin D supplementation.

Data Analysis

Epi Info version 3.4.3 downloaded from the Centers for Disease Control and Prevention (CDC) Web site was used to calculate and complete height for age, weight for age, BMI z scores, and percentiles. BMD was also normalized for age and sex by use of z scores according to the manufacturer's normative data (Hologic QDR 4500C). Low BMD was defined according to a z score less than or equal to 2 SD from the age- and sex-matched reference (1,10).


To show the relations between the primary outcome variables and the secondary outcome variables, a multivariate analysis was used. To correct for the potential confounding effects of differences in bone dimensions on BMD, our multivariate analysis included correction for differences in bone surface area and bone age in all models examining relations to BMD. Microsoft Office Excel 2003 (Microsoft, Redmond, WA) was used to calculate descriptive statistics (mean, minimum, maximum and standard deviation [SD]). Statistical analysis was performed using Statistical Analysis Software version 9.1 (SAS Inc, Cary, NC). P < 0.05 were considered statistically significant. A paired 2-tailed t test was used to test the differences between groups with parametric data. For nonparametric data, the Wilcoxon test was used to test the difference between 2 groups.


The mean age of diagnosis for celiac disease was 9.6 ± 3.7 years (range 3.3–16.1 years). Sixty patients presented with symptoms (the majority being gastrointestinal) and 14 were asymptomatic at diagnosis. The main reason for screening in the latter group was a known family history of celiac disease (n = 12). The patient population was within the normal range expected for nutritional indices with a mean weight for age z score of −0.40 ± 1.15 (range −3.22–2.16) and a height for age z score of −0.15 ± 1.14 (range −2.79–2.07). Table 1 shows age at diagnosis, height, height for age z score, weight, weight for age z score, BMI, BMI z score, as well as relevant biochemical values where available. On average at diagnosis the screening aTTG was 302.6 ± 521.7 U/mL (range 0.8–2230 U/mL) and this was not significantly different from the aTTG at the time of DXA scan 266.8 ± 523.5 U/mL (range 0.8–2230 U/mL). Asymptomatic patients tended to have a lower aTTG compared with symptomatic patients both at diagnosis (90.8 vs 341 U/mL, P < 0.005) and at the time of DXA scan (74.5 vs 301.5 U/mL, P < 0.005). Serum vitamin D (25-hydroxyvitamin D) was measured in 43 patients (8 without symptoms and 35 with symptoms); mean serum values were 78 ± 28.0 nmol/L (20–138.00). In 26 cases the total value was below 80 nmol/L, demonstrating vitamin D levels insufficient for bone health within 60% of the population (25% of those without symptoms and 56% of those with symptoms).

Anthropometric, demographic data, and biochemical data at baseline and follow-up

Seventy-four patients (9.5 ± 3.9 years, range 3.3–16.1 years) received a baseline DXA scan 0.12 ± 0.1 years (range 0.0–0.52) following diagnosis; 29 patients (8.5 ± 3.5 years, range 3.6–16.1) received a follow-up DXA scan 1.7 ± 0.7 years (range 0.6–2.9) following diagnosis. Although the mean age was different between the 2 groups (9.5 vs 8.5 years), this difference was not significant (P > 0.05). In Figure 1, lumbar DXA examinations show that 12 children (16.5%) had a z score of less than or equal to −2 SD at baseline. In the 60 children who reported symptoms at diagnosis, 10 (16.7%) had a z score of less than or equal to −2 SD. In the 14 asymptomatic children 2 (14.3%) had a z score less of than or equal to −2 SD. Baseline spine BMD z score was not significantly different between asymptomatic and symptomatic individuals (−1.1 vs −0.96, P = 0.37). Additional bone health indicator values are shown in Table 2.

FIG. 1:
Bone mineral density (BMD) z scores in children experiencing gastrointestinal symptoms (n = 60) and asymptomatic children (n = 14) at baseline.
Bone health indicators measured at baseline and follow-up

Mean lumbar BMD z score values of those patients with both a baseline and follow-up DXA scan (n = 29) were −1.4 ± 1.0 (range −1.6–1.8) SD and at follow-up −1.3 ± 0.8 (range −2.6–0.7) SD. In the time from baseline to follow-up in these 29 patients the percentage change for lumbar BMD (g/cm2) over time was 9.6%/year. This indicates active bone accrual. The lack of a corresponding change in bone density z score may reflect a delay in catch up in pubertal development despite commencing a gluten-free diet, indicated and supported by no change in the average bone age (7.6 vs 8.6 years, P = 0.40) during the 2 time points for this group.

Univariate analysis showed that lumbar BMD was positively correlated to BMI (P < 0.0001; r2 = 0.35) and bone surface area (P < 0.0001; r2 = 0.76). When adjusted for potential confounding effects of bone surface area and bone area, BMC lumbar was positively correlated with bone surface area (P < 0.0001; r2 = 0.90), age at diagnosis (P < 0.001; r2 = 0.67), bone age (P < 0.001; r2 = 0.74), and BMI (P < 0.001; r2 = 0.34). In multivariate analysis BMD (r2 = 0.86) was positively correlated with bone age (P = 0.009), BMI (P = 0.05) and bone surface area (P = 0.02). Bone mineral content (r2 = 0.92) was positively correlated with BMI (P = 0.02), bone surface area (P < 0.0001), and sex (P = 0.004).


The known association between celiac disease and low bone mass is a particular concern for children and adolescents given the critical bone mass accrual that occurs during this period of rapid growth and development. This study investigated the prevalence of metabolic bone disease in children and adolescents with celiac disease, living in northern Alberta and found a high prevalence of low bone density approaching 16% or more of children newly diagnosed with celiac disease, regardless of symptoms at presentation.

The finding that both symptomatic and asymptomatic children with celiac disease have reduced bone mass at diagnosis is an important issue that has been addressed in few previously reported studies (8,11). Increased awareness of the potential silent and atypical presentations of celiac disease may be an essential component to ensure adequate time for bone accrual in this population. We regard the present study as important to encourage timely screening, diagnosis, and follow-up of young children with celiac disease in regard to restoration and maintenance of these individuals' bone health.

In this study, it was shown that younger age at diagnosis was positively correlated with lumbar BMD. Other studies have also identified that with earlier age of diagnosis and commencement of a gluten-free diet, greater gains in bone recovery can be observed (8,12,13). This is especially important given that, as we have shown, both symptomatic and asymptomatic children have reduced bone mass at diagnosis. Diagnosis is most often delayed in those individuals without gastrointestinal symptoms unless screening for risk factors or atypical symptoms is considered. Earlier diagnosis in this susceptible population will offer more time for critical bone accrual during the bone building years. Certainly a younger age at diagnosis is recognized to have many health benefits in patients with celiac disease, such as reduced risk of associated autoimmune disorders and improved compliance (14).

It was previously demonstrated that there may be significant increases in bone mass in patients with celiac disease diagnosed during childhood and adolescence (8,12,13,15,16). In contrast, however, significant bone accrual in those diagnosed as adults is not always observed (17–19). The main reason thought to explain this finding has been lack of strict, long-term compliance with a gluten-free diet. However, a reduction in time to meet critical bone gains because of late diagnosis is a factor that must be considered. We believe earlier diagnosis of celiac disease in childhood will offer more time for critical bone accrual during the bone building years and as such, standardized screening procedures for individuals at risk of celiac disease are much needed.

Although many studies have shown a relation between celiac disease and poor bone health in adult patients and only more recently in pediatric patients, no prior studies have examined the bone health of children living in northern climates and diagnosed with celiac disease. Consistent with other published studies, we have found the average bone density of children and adolescents with celiac disease to be more than 1 SD below that expected for age and sex, a highly significant reduction in bone mass (13,19). As we would have expected, we also found vitamin D deficiency to be prevalent in this northern population (20). The role of vitamin D deficiency in the etiology of low bone mass in adults with celiac disease remains controversial. Although some studies report vitamin D levels to be in the normal range clearly, some individuals had vitamin D levels that we would now consider a compromise to bone health, particularly in growing children (17,18,20,21). A single study in adults attempted to randomly assign patients to vitamin D and calcium supplements and did not find bone mass increased over and above that achieved by a gluten-free diet alone (17). However, the sample size was clearly inadequate and the role of vitamin D supplementation particularly for children with celiac disease remains unclear. In the present study, we were unable to show a relation between vitamin D levels and bone mass. Unfortunately, vitamin D was measured in a few patients only and according to physician inclination, and so firm conclusions cannot be drawn. Further investigation of the role of both vitamin D deficiency and vitamin D supplementation in the bone health of children with celiac disease, particularly in northern climates, is warranted.

Although this study was not intended to assess longitudinal changes of bone density in the population over time, the 29 patients who received a DXA scan at baseline and follow-up demonstrated no significant change in bone mass for age and sex. This subgroup had lower mean lumbar BMD z score values than the entire group of patients initially, and so the changes observed may not be representative of the population as a whole. In pediatric studies to date reported improvement in bone mass after implementation of a strict gluten-free diet varies. Some authors report minimal short-term gains (12,15), whereas others report complete resolution of osteopenia within as short a time frame as 1 year (8,16). A retrospective study such as ours will not clarify this issue. The longest prospective study to date indicates that more than 5 years on a gluten-free diet is associated with normal bone density in children with celiac disease (22). In adults, physiological bone metabolism does not promote a positive balance of bone accrual, so the potential for bone recovery is more limited. However, it is now clear that individuals diagnosed with celiac disease during childhood can restore compromised bone mass after some period of time on a gluten-free diet. Again, this highlights the importance of early diagnosis in the pediatric population.

Although this study was successful in showing a high prevalence of low BMD in this population, it is not without limitations. Many of these limitations relate to the retrospective nature of the study and in particular that many desired variables, such as vitamin D levels, were not measured. In addition, because bone health is profoundly affected by nutritional intake, access to food records may have also helped draw important conclusions about bone health in this population. Future studies would benefit from prospectively collecting data on pubertal age, dietary intake, cytokines, and other inflammatory markers, serological markers such as vitamin D, vitamin K, and parathyroid hormone. Further examination of longitudinal changes in bone health in this northern population would also provide important information regarding bone disease risk specifically in this population.

In conclusion, BMD is similarly reduced at diagnosis when comparing between children with symptoms and without symptoms. Routine evaluation of BMD in children with celiac disease is important to prevent long-term complications associated with poor bone health. This is imperative when we consider that bone mass is likely to at least track into adulthood or even deteriorate further if diagnosis is delayed (7). Therefore, given delays in diagnosis, osteoporosis becomes a significant health burden for adults diagnosed with celiac disease. It is important that acceptable screening techniques, guidelines, and treatment programs are developed and made available for pediatric patients with celiac disease to ensure optimal health, including bone health, into adulthood.


The authors thank Andrea Patrick and the patients at the gastroenterology clinic at the Stollery Children's Hospital.


1. 2007 Official Positions & Pediatric Official Positions of the International Society for Clinical Densitometry. Accessed July 20, 2009.
2. Fasano A, Catassi C. Current approaches to diagnosis and treatment of celiac disease: an evolving spectrum. Gastroenterology 2001; 120:636–651.
3. Hartman C, Hino B, Lerner A, et al. Bone quantitative ultrasound and bone mineral density in children with celiac disease. J Pediatr Gastroenterol Nutr 2004; 39:504–510.
4. Pazianas M, Butcher GP, Subhani JM, et al. Calcium absorption and bone mineral density in celiacs after long term treatment with gluten-free diet and adequate calcium intake. Osteoporos Int 2005; 16:56–63.
5. Hollis BW. Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin D. J Nutr 2005; 135:317–322.
6. Berti I, Horvath K, Green P, et al. Differences in celiac disease clinical presentation among pediatric and adult relatives of CD patietns in USA. J Invest Med 2000; 48:215A.
7. Bailey DA. The Saskatchewan Pediatric Bone Mineral Accrual Study: bone mineral acquisition during the growing years. Int J Sports Med 1997; 18(suppl 3):S191–S194.
8. Kavak US, Yuce A, Kocak N, et al. Bone mineral density in children with untreated and treated celiac disease. J Pediatr Gastroenterol Nutr 2003; 37:434–436.
9. Mora S. Celiac disease: a bone perspective. J Pediatr Gastroenterol Nutr 2003; 37:409–411.
10. Kanis JA. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group. Osteoporos Int 1994; 4:368–381.
11. Szathmari M, Tulassay T, Arato A, et al. Bone mineral content and density in asymptomatic children with coeliac disease on a gluten-free diet. Eur J Gastroenterol hepatol 2001; 13:419–424.
12. Scotta MS, Salvatore S, Salvatoni A, et al. Bone mineralization and body composition in young patients with celiac disease. Am J Gastroenterol 1997; 92:1331–1334.
13. Tau C, Mautalen C, De Rosa S, et al. Bone mineral density in children with celiac disease. Effect of a gluten-free diet. Eur J Clin Nutr 2006; 60:358–363.
14. Ventura A, Magazzu G, Greco L. Duration of exposure to gluten and risk for autoimmune disorders in patients with celiac disease. SIGEP Study Group for Autoimmune Disorders in Celiac Disease. Gastroenterology 1999; 117:297–303.
15. Mora S, Weber G, Barera G, et al. Effect of gluten-free diet on bone mineral content in growing patients with celiac disease. Am J Clin Nutr 1993; 57:224–228.
16. Barera G, Beccio S, Proverbio MC, et al. Longitudinal changes in bone metabolism and bone mineral content in children with celiac disease during consumption of a gluten-free diet. Am J Clin Nutr 2004; 79:148–154.
17. Mautalen C, Gonzalez D, Mazure R, et al. Effect of treatment on bone mass, mineral metabolism, and body composition in untreated celiac disease patients. Am J Gastroenterol 1997; 92:313–318.
18. Ciacci C, Maurelli L, Klain M, et al. Effects of dietary treatment on bone mineral density in adults with celiac disease: factors predicting response. Am J Gastroenterol 1997; 92:992–996.
19. Valdimarsson T, Toss G, Lofman O, et al. Three years' follow-up of bone density in adult coeliac disease: significance of secondary hyperparathyroidism. Scand J Gastroenterol 2000; 35:274–280.
20. Roth DE, Martz P, Yeo R, et al. Are national vitamin D guidelines sufficient to maintain adequate blood levels in children? Can J Public Health 2005; 96:443–449.
21. Weaver CM. Vitamin D, calcium homeostasis, and skeleton accretion in children. J Bone Miner Res 2007; 22(suppl 2):V45–V49.
22. Mora S, Barera G, Beccio S, et al. Bone density and bone metabolism are normal after long-term gluten-free diet in young celiac patients. Am J Gastroenterol 1999; 94:398–403.

Adolescents; Bone mineral density; Celiac disease; Children

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