Original Full Length ArticleSignificant bone microarchitecture impairment in premenopausal women with active celiac disease
Introduction
Celiac disease (CD) is a gluten-dependent systemic disorder characterized by an autoimmune damage initiated in the small bowel of predisposed individuals [1]. Previous studies have shown that osteopenia and osteoporosis are well-recognized complications in CD patients [2], [3], [4], [5], [6], [7], [8], [9]. Bone disease constitutes a major problem through the association with an increased risk of bone fractures, predominantly in the peripheral skeleton and often produced by minimal or moderate trauma [10]. In such context, former studies have shown that the distal radius is the most common fractured site corresponding to more than 50% of events in CD cases [10], [11], [12], [13], [14]. Although controversial, some studies suggest that the increased risk can be reverted by strict adherence to a specific treatment, the gluten-free diet (GFD) [11], [12], [15].
Bone health, characterized by its mass, density, and microarchitectural and material properties, is maintained by a balanced system of remodeling [9], [16], [17]. The deterioration of any of those parameters or an uncoupling of the remodeling process, leads to bone fragility and an increased risk of fractures. Osteoporosis is characterized by low bone mass, thin porous cortices and decreased trabecular number and connectivity [17]. It may be diagnosed before fractures occur by measuring areal bone mineral density (aBMD) using dual energy X-ray absorptiometry (DXA) [18]. Thus, DXA has been considered the gold standard for predicting osteoporotic fractures. Despite the ability of DXA to assess bone mass (BMC, BMD), the inherent planar nature of the measurements makes geometric assessment of a bone impossible and bone strength estimation very limited. Furthermore, the method is unable to discriminate between trabecular and cortical bone tissues, which have been shown to be differentially affected by many conditions [19], [20]. Furthermore, DXA cannot assess the microarchitectural structure of bones and, therefore, explore the intimate pathogenesis of osteoporotic fractures. High resolution peripheral quantitative computed tomography (HR-pQCT), which is a non-invasive method for volumetric three-dimensional characterization of peripheral skeletal sites, allows quantification of bone microarchitecture parameters and permits the assessment of bone mechanical properties by FEA (Finite element analysis) [21], [22], [23]. For this purpose, the resolution of HR-pQCT (82 μm) permits the direct and reliable assessment of microarchitectural parameters which are relevant to bone strength. Hence, HR-pQCT has shown to provide better prediction of bone strength when compared with DXA [24].
Some years ago, our group conducted a longitudinal analysis of bone structure and strength in a series of newly diagnosed CD patients using peripheral and axial quantitative computerized tomography (QCT) [25]. That seminal study allowed us to speculate about the pathogenesis of bone weakening in CD patients. There, we suggested that secondary hyperparathyroidism and the inflammatory process of CD would enhance bone remodeling inducing trabecular thinning, cortical–subcortical bone mass loss, increase of intracortical porosity and impairment of bone mechanical quality.
To our knowledge, no studies have assessed the microarchitectural quality of bones in CD patients. Therefore, our aims in this study were: 1—to determine the microarchitectural characteristics of peripheral bones in a consecutive series of adult premenopausal women with active CD assessed at the time of diagnosis using HR-pQCT and 2—to compare these results with those of healthy women of similar age and body mass index (BMI). Secondary aims of the study were to assess the association of the clinical phenotype at diagnosis with the severity of bone impairment.
Section snippets
Patients and controls
Female patients with newly diagnosed CD were recruited at a single center (Sección Intestino Delgado, Hospital de Gastroenterología “Dr. C. Bonorino Udaondo”). Between May 2011 and November 2012, 67 consecutive female patients with recent diagnosis of CD were screened for inclusion and exclusion criteria. We defined premenopausal status on a clinical basis: less than one year since last menstrual cycle. Patients with a concomitant known disorder affecting bone metabolism (thyroid disease,
Clinical features
Untreated CD patients and healthy controls were comparable in terms of height, body weight and BMI (p NS) (Table 1). Only Six CD patients had low weight, with a BMI less than 18, 5. While 22 patients had a symptomatic clinical presentation, nine cases were considered as having subclinical CD (two diagnosed by case finding among 1st degree relatives, three in the investigation of microcytic anemia and four in the endoscopic investigation because of gastroesophageal reflux symptoms). All of these
Discussion
A series of recent studies and a meta-analysis have shown that CD patients have an increased incidence of bone fractures, mostly in the peripheral skeleton [10], [11], [12], [13], [14], [15], [16]. Such risk is associated with the symptomatic clinical phenotype at the time of diagnosis, is related to low trauma (osteoporotic fractures), is mainly produced before diagnosis and, finally, may be recurrent in a subset of patients [9], [10], [11], [12], [13], [14], [15]. In this context, studies
Conclusion
In conclusion, the present study provides insight into the pathogenesis of bone mass loss in CD patients. In this group of young women with newly diagnosed celiac disease, HRpQCT allowed us to detect a severe compromise of both, volumetric density and bone microarchitecture. To our knowledge, this is the first time that HR-pQCT has described characteristics of bone microarchitecture deterioration in CD patients. In the prospective follow-up of this group of patients we expect to be able to
Disclosures
All authors state that they have no conflicts of interest.
Acknowledgments
We thank Susana Carballo for editing the English language of the manuscript.
The study was partially funded by: 1—Consejo de Investigación en Salud; Ministerio de Salud; Gobierno de la Ciudad de Buenos Aires.
2—FIM, Fundación de Investigaciones Metabólicas.
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