Osteoporosis in celiac disease and in endocrine and reproductive disorders.

As the increase in lifespan brings to light diseases that were previously not clinically detectable, osteoporosis has become an issue of worldwide significance. The disease is marked by a loss of bone mass; the bones become less dense, fragile and more prone to fracturing. Because it is regulated by endocrine and environmental factors, osteoporosis presents a multifactorial etiopathogenesis, with the genetic component accounting for 70% of an individual variation in bone mass density (BMD), the principal determinant, with age, of fracture risk. Pathological conditions such as celiac disease (CD) exacerbate the process of bone loss, so that the occurrence of osteoporosis in celiac subjects is of particular note: indeed, the screening of osteoporosis patients for this disease is advisable, since it may be the only sign of undiagnosed CD. An increase in interleukin IL-1beta, of the IL-1 system, in the relatives of celiac patients confirms the genetic predisposition to osteoporosis and its presence is evidence of an association between the two conditions. The direct effect on the bones of CD is secondary to poor absorption of calcium and vitamin D. In women osteoporosis is indirectly associated with early menopause and amenorrhea, and it may follow prolonged breast-feeding and frequent pregnancies, while in men it is associated with hypogonadism and GH deficit. These endocrine and non-endocrine factors exert their effects on bones by modulating the RANK/RANK-L/OPG system. An appropriate lifestyle from adolescence onwards, together with early diagnosis of and treatment for CD and primary and secondary endocrine pathologies are important for the prevention of damage to the bones.

Risk of osteoporosis in endocrine disorders and celiac disease.

Osteoporosis is characterized by a loss of bone mass; the bones become less dense, fragile and prone to fracturing. It is regulated by endocrine-environmental factors with the genetic component accounting for 70% of an individual's variation in bone mass density (BMD). Pathological conditions such as celiac disease (CD) exacerbate the process of bone loss and the presence of osteoporosis in celiac subjects may be the only sign of undiagnosed CD. The interleukins IL-1alpha and IL-1beta are stimulators of bone resorption; the relatives of celiac patients shown the increased IL-1beta supporting the genetic susceptibility. In women osteoporosis is indirectly associated with early menopause and amenorrhea, while in men it is associated with hypogonadism and GH deficit. The direct effect on the bones of CD is secondary to poor absorption of calcium and vitamin D. These endocrine and non-endocrine factors exert their effects on bones by modulating the RANK/RANK-L/OPG system.

[Reproductive aspects of celiac disease]. / Aspetti riproduttivi della malattia celiaca.

In the past, celiac disease (CD), or intolerance to gluten, was considered a rare disease of infancy characterized by chronic diarrhea with malabsorption and delayed growth. Besides the overt enteropathy, there are other clinic and subclinical forms which appear later in life. Target organs are not limited to the gut, but include liver, thyroid, skin and female and male reproductive systems. CD interference on reproduction is related to the multifactorial nature of the disease, whose pathological manifestations can be modulated, besides gluten, by different concurrent genetic and environmental factors. CD induces malabsorption with consequent deficiencies of micronutrients such as iron, folic acid and vitamin K, which are essential for organogenesis, and fat-soluble vitamins important for spermatogenesis. Regarding endocrine disorders, the deficiencies of specific trace elements on ovarian function could explain its involvement in the increased risk of female osteoporosis in CD patients. Affected males show a picture of tissue resistance to androgens; the increases of follicle-stimulating hormone and prolactin, not associated with infertility, may indicate an imbalance at hypothalamus-pituitary level, with general effects on health. Since reproductive alterations are reversible, adoption of a gluten-free diet supported by early diagnosis is important. Therefore, the detection of early biomarkers, such as deficiencies of vitamins and/or iron and andrological or endocrinological dysfunctions, should trigger timely strategies for prevention and treatment.

Selenium status and over-expression of interleukin-15 in celiac disease and autoimmune thyroid diseases.

In celiac disease (CD), for its multifactorial nature, the target organs are not limited to the gut, but include thyroid, liver, skin and reproductive and nervous systems. Between the extraintestinal symptoms associated with CD, autoimmune thyroid diseases (AITDs) are more evident, underlining as CD-related autoimmune alterations can be modulated not only by gluten but also by various concurrent endogenous (genetic affinity, over-expression of cytokines) and exogenous (environment, nutritional deficiency) factors. In their pathogenesis a central role for over-expression of interleukin-15 (IL-15) is shown, by inhibiting apoptosis, leading to the perpetuation of inflammation and tissue destruction. Thyroid is particularly sensitive to selenium deficiency because selenoproteins are significant in biosynthesis and activity of thyroid hormones; besides, some selenoproteins as glutathione peroxidase are involved in inhibiting apoptosis. Thus, selenium malabsorption in CD can be thought as a key factor directly leading to thyroid and intestinal damage. Considering the complexity of this interaction and on the basis of available evidence, the aim of this review is to assess as preventive and therapeutic target the role of IL-15 and selenium in the pathogeneses of both CD and AITD.