Mário Rui Mascarenhas

Vitamin D supplementation guidelines

Research carried out during the past two-decades extended the understanding of actions of vitamin D, from regulating calcium and phosphate absorption and bone metabolism to many pleiotropic actions in organs and tissues in the body. Most observational and ecological studies report association of higher serum 25-hydroxyvitamin D [25(OH)D] concentrations with improved outcomes for several chronic, communicable and non-communicable diseases. Consequently, numerous agencies and scientific organizations have developed recommendations for vitamin D supplementation and guidance on optimal serum 25(OH)D concentrations. The bone-centric guidelines recommend a target 25(OH)D concentration of 20ng/mL (50nmol/L), and age-dependent daily vitamin D doses of 400-800IU. The guidelines focused on pleiotropic effects of vitamin D recommend a target 25(OH)D concentration of 30ng/mL (75nmol/L), and age-, body weight-, disease-status, and ethnicity dependent vitamin D doses ranging between 400 and 2000IU/day. The wise and balanced choice of the recommendations to follow depends on ones individual health outcome concerns, age, body weight, latitude of residence, dietary and cultural habits, making the regional or nationwide guidelines more applicable in clinical practice. While natural sources of vitamin D can raise 25(OH)D concentrations, relative to dietary preferences and latitude of residence, in the context of general population, these sources are regarded ineffective to maintain the year-round 25(OH)D concentrations in the range of 30-50ng/mL (75-125nmol/L). Vitamin D self-administration related adverse effects, such as hypercalcemia and hypercalciuria are rare, and usually result from taking extremely high doses of vitamin D for a prolonged time.

ACP1 genotype, glutathione reductase activity, and riboflavin uptake affect cardiovascular risk in the obese

Erythrocyte acid phosphatase (ACP locus 1), also known as low-molecular-weight protein tyrosine phosphatase, has previously been associated to glycemia, dyslipidemia, and obesity. In this study, ACP1 genotype and activity were tested in 318 women aged 19 to 83 (mean, 51.74 +/- 13.44) years. ACP1 genotype was found to directly correlate to glutathione reductase activity (P < .001) and levels of low-density lipoprotein cholesterol (P = .038). Glutathione reductase activity was in turn found to correlate to a series of cardiovascular risk factors such as systolic arterial pressure (P < .001), total cholesterol levels (P = .018), and low-density lipoprotein cholesterol levels (P = .039). A possible protective effect of ACP1 genotype AA against these cardiovascular risk factors was observed in this study. Furthermore, this work hypothesizes that nutritional riboflavin uptake becomes more crucial as body mass index increases, to counteract oxidative stress and minimize cardiovascular risk. This might be especially true in ACP1 genotypes AC, BC, and CC, which might possibly show the least endogenous protection against oxidative stress.

A WNK4 gene variant relates to osteoporosis and not to hypertension in the Portuguese population.

Germline mutations in the WNK4 gene originate Gordon syndrome or pseudohypoaldosteronism type II, a familial form of hypertension with hyperkalemia and hypercalciuria. In order to elucidate the contribution of WNK4 genetic variants to hypertension and/or osteoporosis, we analyzed 271 control individuals and a cohort of 448 hypertensive and 372 osteoporosis patients from the Portuguese population. Ten genetic variants were detected in 4.3% of the population under study, none of which revealed any significant association to the hypertension phenotype. In contrast, a rare missense alteration within exon 17 in a highly conserved arginine residue showed a possible tendency for association to the osteoporosis group. Our data suggest that WNK4 polymorphism rs56116165 is a rare allelic variant in a candidate gene with a biological function in renal calcium homeostasis that may contribute to a genetic predisposition to osteoporosis.

A case of thyroid hormone resistance: a rare mutation

Reduced sensitivity to thyroid hormones (RSTH) is a rare disease that affects about 3,000 individuals, belonging to about 1,000 families. It results from reduced intracellular action of thyroid hormones (TH) genetically determined and manifests as persistent hyperthyroxinemia with non-suppressed thyroid-stimulating hormone (TSH). We describe a 67-years old, Caucasian woman, with past history of subtotal thyroidectomy due to diffuse goiter, who presents with a recurrence of goiter. Although she is clinically euthyroid, laboratory evaluation shows persistent hyperthyroxinemia with non-suppressed TSH. Response to thyrotropin releasing hormone (TRH) test was normal and TSH concentrations were not suppressed during oral administration of suprafisiologic doses of levothyroxine (L-T4). Peripheral blood DNA was extracted from the patient and a mutation was found localized in cluster one, at codon 346 of the ligand binding domain of the THRB gene. The patients son underwent thyroid function testing (TFT) and genetic study, both negative, suggesting a sporadic mutation. RSTH should be considered in all hyperthyroxinemic patients who are clinically euthyroid. Mutations interfering with three major steps required for TH action on target tissues have been, so far, identified (TR-β, TR-α, MCT8, SPB2). Each mutation is associated with a distinctive syndrome. Goal of management is to maintain a normal serum TSH level and a eumetabolic state and offer appropriate genetic counselling and prenatal diagnosis. Inappropriate treatment of eumetabolic patients results in hypothyroidism and need for TH replacement.

Prevalence of silent vertebral fractures detected by vertebral fracture assessment in young Portuguese men with hyperthyroidism.

BACKGROUND Hyperthyroidism is a risk factor for reduced bone mineral density (BMD) and osteoporotic fractures. Vertebral fracture assessment (VFA) by dual-energy X-ray absorptiometry (DXA) is a radiological method of visualization of the spine, which enables patient comfort and reduced radiation exposure. OBJECTIVES This study was carried out to evaluate BMD and the prevalence of silent vertebral fractures in young men with hyperthyroidism. DESIGN We conducted a cross-sectional study in a group of Portuguese men aged up to 50 years and matched in hyperthyroidism (n=24) and control (n=24) groups. MATERIALS AND METHODS A group of 48 Portuguese men aged up to 50 years was divided and matched in hyperthyroidism (n=24) and control (n=24) groups. BMD (g/cm(2)) at L1-L4, hip, radius 33%, and whole body as well as the total body masses (kg) were studied by DXA. VFA was used to detect fractures and those were classified by Genants semiquantitative method. No patient had previously been treated for hyperthyroidism, osteoporosis, or low bone mass. Adequate statistical tests were used. RESULTS The mean age, height, and total fat mass were similar in both groups (P≥0.05). The total lean body mass and the mean BMD at lumbar spine, hip, and whole body were significantly decreased in the hyperthyroidism group. In this group, there was also a trend for an increased prevalence of reduced BMD/osteoporosis and osteoporotic vertebral fractures. CONCLUSIONS The results obtained using VFA technology (confirmed by X-ray) suggest that the BMD changes in young men with nontreated hyperthyroidism may lead to the development of osteoporosis and vertebral fractures. This supports the pertinence of using VFA in the routine of osteoporosis assessment to detect silent fractures precociously and consider early treatment.

Abstracts of the III International symposium “Diseases of the bones and joints and the age” (March 12–14, 2018, Lviv, Ukraine)

The actual increase in human longevity is possible due to the public health care and to the treatment of several chronic diseases, mainly in the oldest people. However, some of those drugs may have negative effects on the skeleton, not only decreasing bone mass, but also increasing the risk for fragility fractures. Osteoporosis is the most prevalent metabolic bone disease. It is characterized by a deterioration of bone microarchitecture and consequent fragility fractures. It is a heterogeneous and multifactorial etiological disease. About 20 to 30 % of osteoporotic postmenopausal women and more than 50 % men have a secondary induced etiology, namely the medications.

Bone Mass in Anorexia Nervosa and Thin Postmenopausal Women-Related Secondary Amenorrhea

1.1 Bone mass acquisition in normal teenagers The first three years of life seem to be very important in the skeleton bone mass apposition. The bone mineral density (BMD) increases during childhood, but the maximum increment occurs in the critical phase of growth, reaching a plateau at the end or after the puberty in girls as well as in boys (Theintz et al., 1992; Bachrach, 2001; Schoenau et al., 2001). Bone mass increases as the bone size increase. In females, BMD is increased rapidly after 11 years of age and reaches maximum at around the age of 13-14 years or quickly after menarche. Until the age of 18 years, about 90% of the peak bone mass has been acquired. At puberty, there is an acceleration of bone mineralization, especially of the trabecular bone and by the end of sex maturation it is more than twice as compared with that at the pubertal onset (Theintz et al., 1992; Bailey, 1999). In general, the girls have a greater BMD than boys in the first half of the second decade of life. During the intermediate stage of puberty (Martin et al., 1997), the bone mineral content (BMC) and the bone thickness are lower in girls, thus predisposing women to a higher complication risk of reduced BMD (Baroncelli & Saggese, 2000). Nutrition, body weight and total body lean mass are determinants of the bone mass in adolescent girls. Calcium intake is essential for optimization of the bone mass acquisition in healthy pubertal adolescents (Garcia e Costa et al., 1995). The accumulation of calcium in the skeleton varies with the daily intake and 1200