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Osteoporosis In Non-Celiac Wheat Sensitivity Patients

Completed
Conditions
Non-celiac Wheat Sensitivity
Registration Number
NCT02421783
Lead Sponsor
University of Palermo
Brief Summary

Non-celiac gluten sensitivity (NCGS) or 'wheat sensitivity' (NCWS) is included in the spectrum of gluten-related disorders. No data are available on the prevalence of low bone mass density (BMD) in NCWS. Our study aims to evaluate the prevalence of low BMD in NCWS patients and search for correlations with other clinical characteristics.

This prospective observation study will include 90 NCWS patients with irritable bowel syndrome (IBS)-like symptoms, 90 IBS and 90 celiac controls. Patients will be recruited at the Internal Medicine and at the Gastroenterology Units of the University of Palermo. Elimination diet and double-blind placebo controlled (DBPC) wheat challenge proved the NCWS diagnosis. All subjects underwent BMD assessment by Dual Energy X-Ray Absorptiometry (DXA), duodenal histology, Human Leukocyte Antigen (HLA) DQ typing, body mass index (BMI) evaluation and assessment for daily calcium intake.

Detailed Description

Celiac disease (CD) has been reported to increase the risk of osteoporosis, with a resulting augmented risk of fractures. More recently, it has been reported that a consistent percentage of the general population consider themselves to be suffering from problems caused by wheat and/or gluten ingestion, even though they do not have CD or wheat allergy. This clinical condition has been named Non-Celiac Gluten Sensitivity' (NCGS). In a previous paper the investigators suggested the term 'Non-Celiac Wheat Sensitivity' (NCWS), since it is not known what component of wheat causes the symptoms in NCGS patients, and the investigators also showed that these patients had a high frequency of coexistent multiple food hypersensitivity. That previous study also showed a percentage of NCWS patients had weight loss and anemia: whether these depended on the intestinal malabsorption or not remains unclear. As yet no data are available on the presence and prevalence of low bone mass density (BMD) in NCWS patients. The aims of the present study is: 1) to investigate the prevalence of low BMD in NCWS patient and 2) to search for a possible correlation between BMD and other clinical characteristics, in particular the body mass index (BMI), of NCWS patients.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
270
Inclusion Criteria

To diagnose NCWS the recently proposed criteria will be adopted. All the patients will meet the following criteria:

  • negative serum anti-transglutaminase (anti-tTG) and anti-endomysium (EmA) immunoglobulin (Ig)A and IgG antibodies;
  • absence of intestinal villous atrophy;
  • negative IgE-mediated immune-allergy tests to wheat (skin prick tests and/or serum specific IgE detection);
  • resolution of the IBS symptoms on standard elimination diet, excluding wheat, cow's milk, egg, tomato, chocolate, and other self-reported food(s) causing symptoms;
  • symptom reappearance on double-blind placebo-controlled (DBPC) wheat challenge. As the investigators previously described in other studies, DBPC cow's milk protein challenge and other "open" food challenges will be performed too.

Additional inclusion criteria will be:

  • age >18 years; follow-up duration longer than six months after the initial diagnosis;
  • at least two outpatient visits during the follow-up period.
Exclusion Criteria
  • positive EmA in the culture medium of the duodenal biopsies, also in the case of normal villi/crypts ratio in the duodenal mucosa;
  • self-exclusion of wheat from the diet and refusal to reintroduce it, before entering the study;
  • other "organic" gastrointestinal disorders;
  • nervous system disease and/or major psychiatric disorder;
  • physical impairment limiting physical activity;
  • menopause;
  • steroid and sex steroid therapy, hormone replacement therapy or ovariectomy.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Change in bone mineral density (BMD)At baseline and at 24 months

BMD will be assessed by dual x-ray absorptiometry (DXA), using a QDR Discovery Hologic DXA scanner in the femoral neck and in the lumbar spine. For each scan, BMD and T-scores will be recorded. A T-score between +1 and -1 is considered normal, between -1 and -2.5 indicates osteopenia, -2.5 or lower indicates osteoporosis. The investigators also will calculate the 10-year fracture risks according to the standardized WHO FRAX equation, computed with BMD (T-score) at the femoral neck.

Secondary Outcome Measures
NameTimeMethod
Conventional lateral spine x-ray as an assessment of suspected osteoporotic vertebral fractures, using Genant's methodAt baseline

A random sample of the patients and controls will undergo conventional lateral spine x-ray for better assessment of suspected osteoporotic vertebral fractures, according to Genant's method (grade 0, no reduction; grade 1, minimal fracture, 20-25% vertebral height decrease; grade 2, moderate fracture, 25-40% vertebral height decrease; and grade 3, severe fracture, greater than 40% vertebral height decrease).

Change in urinary phosphorus levelsAt baseline and at 24 months

Urinary phosphorus levels values will be detected (refences values 0.4-1.3 g per 24-hour urine sample).

Change in serum bone alkaline phosphataseAt baseline and at 24 months

Serum bone alkaline phosphatase values will be detected (refences values of adults males \< or =20 mcg/L; of adults premenopausal females \< or =14 mcg/L; of adults postmenopausal females \< or =22 mcg/L).

Change in serum calcium levelsAt baseline and at 24 months

Serum calcium levels values will be detected (refences values of males age 18-21 years: 9.3-10.3 mg/dL, age 22 years and older: 8.9-10.1 mg/dL; of females age 18 years and older: 8.9-10.1 mg/dL)

Change in serum phosphorus levelsAt baseline and at 24 months

Serum phosphorus levels values will be detected (refences values of subjects \> or =18 years: 2.5-4.5 mg/dL).

Change in dietary intake and lifestyleAt baseline and at 24 months

All the participants will fill in a health and lifestyle questionnaire, considering menarche and age at menopause (if applicable), medical and drug abuse history, lifestyle habits (including elimination diet, smoking status, alcohol consumption, Italian espresso coffee drinking and physical activity); history of bone fractures will also be recorded. In order to assess daily caloric intake and calcium intake, the subjects will receive a dietary form containing a printed list of the most common foods.

Change in serum 25-hydroxyvitamin DAt baseline and at 24 months

Serum 25-hydroxyvitamin D values will be detected (refences values 30.0-74.0 ng/mL).

Change in urinary calcium levelsAt baseline and at 24 months

Urinary calcium levels values will be detected (refences values 100-300 mg per 24-hour urine sample).

Trial Locations

Locations (2)

Antonio Carroccio

🇮🇹

Sciacca, Agrigento, Italy

Pasquale Mansueto

🇮🇹

Palermo, Italy

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