The other side of celiac disease – assessment of bone mineral density and body composition in patients with celiac disease

Introduction

Celiac disease (CD) is a chronic, small intestinal enteropathy caused by exposure to gluten among genetically predisposed individuals [1]. The worldwide prevalence of CD is estimated to be 0.7–1.4% of the general population [2]. Recently the clinical presentation of CD has changed, with non-classical CD characterised by extraintestinal manifestation being more common than a classical form of the disease with the domination of gastrointestinal symptoms [3]. Decreased bone mineral density (BMD), which can further develop into osteoporosis, is one of the most frequent extraintestinal symptoms of CD [3, 4]. Osteoporosis is a skeletal disorder characterised by a significant loss of bone mass, contributing to increased bone fragility and a higher risk of bone fractures [5]. Current data report that 30–60% of newly diagnosed patients with CD show decreased BMD, and 18–35% present with osteoporosis [6–9]. The mechanism of osteoporosis in CD is multifactorial and includes such elements as CD-related local and systemic inflammation [10–12] and deficiency of vitamin D together with impaired calcium absorption, leading to secondary hyperparathyroidism and increased bone resorption [13]. Moreover, because CD is an inflammatory disease proceeding with malabsorption, patients at diagnosis present with lower mean body mass index (BMI) than the general population. Interestingly, it has been observed that the nutritional status of CD patients at diagnosis in the last few years is better than that of those diagnosed in previous years. Furthermore, recently more patients at diagnosis have excess body mass: in Western countries, it is estimated that between 15% and 31% of individuals with CD have a BMI indicating overweight at the time of the diagnosis, and 6.8–13% have obesity [14, 15].

According to the World Health Organisation (WHO), the gold standard in the diagnosis of osteoporosis is an examination of BMD on the basis of dual-energy X-ray absorptiometry (DXA): normal: T-score ≥ −1 SD; osteopaenia (low bone mass): T-score < −1 SD and > –2.5 SD; osteoporosis: T-score ≤ –2.5 SD; severe osteoporosis: T-score ≤ –2.5 SD with fragility fractures [16].

In this study, we evaluated the prevalence of osteopaenia and osteoporosis and the status of 25(OH)D and ionised calcium in women with CD and compared them with healthy individuals. Furthermore, we conducted an assessment of body composition parameters in both groups.

Aim

The aim of the study was to investigate BMD, body composition, 25(OH)D, and calcium blood parameters, and to compare them between women with CD and healthy individuals.

Material and methods

The study comprised 58 adult women: 30 women suffering from CD treated in the outpatient clinic of the Department of Gastroenterology, Dietetics, and Internal Medicine of Poznan University of Medical Sciences, and 28 healthy women in the control group (CG). Before starting examinations, all patients provided their written informed consent. The Bioethics Committee of Poznan University of Medical Sciences approved the study protocol – number 824/21. The study was conducted in accordance with the guidelines included in Helsinki Declaration. The diagnosis of CD was based on clinical, histopathological, and serological criteria. The exclusion criteria were as follow: age under 18 years, pregnancy, male sex, non-adherence to a gluten-free diet, the coexistence of diseases that additionally affect the nutritional status and BMD: inflammatory bowel diseases – Crohn’s disease or ulcerative colitis, active neoplastic disease, hyperthyroidism, liver failure, chronic kidney disease, rheumatoid arthritis, chronic obstructive pulmonary disease, and a lack of the written informed consent to participate in the study. All patients included in the study were treated according to the current standards of the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) and European Guidelines on Celiac Disease and Other Gluten-Related Disorders, depending on their clinical status. Densitometric measurements of the lumbar spine (L1–L4) and the femoral neck (FN) were carried out using DXA with Lunar DPX-Plus (Lunar, Inc., Madison, Wisconsin, United States) apparatus. BMD, T-score, and Z-score parameters were obtained to assess skeletal status. The T-score represented the difference between the obtained BMD result and the mean BMD for young adults, divided by the standard deviation (SD) for young adults. The Z-score was calculated as the difference between the measured BMD and the age-adjusted mean BMD divided by the SD in the general population. In both groups, we determined body composition parameters – body mass in kg, BMI, fat %, fat in kg, muscle mass, and fat-free mass (FFM). Body composition analyses were performed in the morning, after a night-long rest, and when fasting. During measurements, the patients were wearing light clothes and no shoes. Body mass was measured with the use of the bioimpedance method (TANITA MC-180) to the nearest 0.01 kg. Additionally, serum 25(OH)D and ionised calcium were determined using, respectively, the electrochemiluminescence binding method test and ion-selective electrode. All patients and controls completed an original questionnaire referring to the supplementation of vitamin D and calcium.

Results

The study involved 30 women with CD and 28 healthy women. 73% of patients were under 50 years of age. The characteristics of the study groups are shown in Table I. Significant differences were found between the groups for body mass, BMI, BMD, T-score and Z-score of the FN, BMD and T-score of the L1-L4, and 25(OH)D concentration. Based on the T-score, patients were divided into groups with normal and decreased BMD – osteopaenia and osteoporosis – of the FN and L1-L4. Statistically significant differences were observed in the prevalence of decreased BMD of the L1-L4 between both groups (p < 0.001) but not of the FN. The prevalence of osteopaenia and osteoporosis based on the T-score was higher in the group of CD patients. None of the patients reported a history of fractures. The outcomes are presented in Tables II and III.

CD patients more often declared supplementation of vitamin D and calcium than participants in the CG. The differences are statistically significant. Table IV shows specific data for supplementation of vitamin D and calcium in the study group. Furthermore, we found that patients with CD supplementing vitamin D had higher serum concentrations of 25(OH)D than the CG (p = 0.019), which is presented in Table V. On the other hand, there was no statistical difference between serum concentrations of ionised calcium in patients supplementing calcium in both groups, but in the CG, only one person declared calcium supplementation (p = 0.99).

Discussion

In the study, decreased BMD affected 23.33–50% of patients with CD depending on the measurement site. According to research, osteopaenia affects 23.33% and 36.67% of patients in the FN and L1-L4, respectively, and osteoporosis in L1-L4 affects 13.33% of patients with CD. There are no cases of osteoporosis in FN. More patients present low BMD in L1-L4 than in FN. Similarly to our results, Lewis et al. reported data on T-score in the lumbar in comparison with the FN. Researchers reported that osteoporosis at the hip affects 7% and at the spine 14% of patients [17]. However, Ganji et al. reported no significant difference between decreased BMD in the femoral and spine in CD; in a group of 76 CD patients aged 20–60 years, 55% had osteopaenia in the FN or spine and 36% had osteoporosis in the FN or spine [18]. A Polish study on premenopausal women and men with CD by Szymczak et al. reported 62.8% of cases of osteopaenia and 20% of osteoporosis in the FN, and 57.2% of cases of osteopaenia, and 28.6% of osteoporosis in the lumbar spine [19]. In 2019, Ganji et al. estimated in a systematic review comprising 563 premenopausal women and men that osteoporosis occurs in 14.4% and osteopaenia in 39.6% of patients [20]. The aetiopathology of osteoporosis in CD is multifactorial. Bone alterations are thought to develop in CD patients mainly due to impaired intestinal absorption efficiency, leading to hypocalcaemia and vitamin D malabsorption. Also, chronic inflammation causing increased production of pro-inflammatory cytokines in the mucosa and serum such as TNF-α, IL-1, and IL-6 disrupt bone growth and autoimmune factors [7, 13]. Data on the incidence of osteopaenia and osteoporosis often vary between studies. When considering these data, the selection of patients for the study group and the coexistence of other risk factors should be taken into account. Furthermore, our study revealed that body mass, BMI, fat tissue, muscle mass, and FFM were lower in the CD patients than in the healthy controls. These outcomes are in line with other studies: patients, independently of following a gluten-free diet (GFD), presented lower body mass, BMI, BMD, bone mineral content, fat mass, and fat-free mass than controls [21]. González et al. in a group of women between 20 and 60 years old, following or not following GFD, observed that CD women had a lower BMI compared to the control group, and women with CD not following a GFD presented a lower BMI than those on a GFD, as well as a lower body fat and fat-free mass than the CG [22]. Here it is worth underlining that CD is characterised by the presence of villous abnormalities, which in turn lead to malabsorption of both macro- and micronutrients. Furthermore, there is a broad spectrum of gastrointestinal manifestations such as diarrhoea that can predispose to decreased intestinal absorption [23]. Paradoxically, there is an increasing group of patients with CD with excess body weight, especially in western countries. A study by Tucker et al. conducted in a group of 187 adults with CD from the UK showed that 44% of them had BMI indicating overweight (31%) or obesity (13%), suggesting that the profile of CD patients is changing, and a broader approach to dealing with patients might be needed [24]. In our study 25% of CD patients had BMI indicating underweight, 64% had normal BMI, and 11% had excess body weight. Moreover, in the conducted study 79.31% of CD patients declared supplementation of vitamin D and 41% declared supplementation of calcium. In a group of healthy controls, only 42.86% declared supplementation of vitamin D and 4.76% (one person) declared supplementation of calcium. Also, serum concentration of 25(OH)D was higher in celiac patients than in healthy controls. The results do not fit with the theory that patients with CD have lower serum concentrations of 25(OH)D, which predispose them to the development of osteoporosis. On the other hand, the serum concentration of calcium was lower in CD patients, but the difference was not statistically significant. Such discrepancies in the frequency of vitamin D supplementation in both groups may be because the CD patients participating in the study were under outpatient care in our clinic, where supplementation of vitamin D and, if necessary, calcium is recommended. Our study has some limitations. First, postmenopausal women were not excluded from the study, but 73% of patients were under 50 years of age; however, the objective was to assess the incidence of osteopaenia and osteoporosis in the entire adult population of women with CD, and can we observe that the medium age of diagnosis is increasing. Although women in the CG were younger than those in the research group, this difference is not statistically significant. Another limitation is the lack of data on the environmental, nutritional, and genetic factors, which might have affected both BMD and the course of the disease. Therefore, further extensive studies referring to these factors are required. Also, it would be valuable to correlate the vitamin D and calcium levels in the examined groups of patients with their BMD. The dose of vitamin D was adjusted in patients with celiac disease based on the results of blood tests by the attending physician. Participants in the control group were not patients of our clinic; therefore, we do not have information on whether the dose of vitamin D was introduced prophylactically or adjusted based on the results of blood tests. Vitamin D blood test is not a routinely ordered test by general practitioners in Poland.

Conclusions

Our study demonstrated that women with CD have decreased BMD and anthropometric parameters: body mass, BMI, fat tissue, muscle mass, and fat-free mass. On the other hand, they present higher 25(OH)D concentration and more often declare supplementing vitamin D and calcium. None of the patients reported a history of fractures.