Osteoporosis and dermatoporosis: a review on the role of vitamin D.

Osteoporosis (OP) and Dermatoporosis (DP) are expressions of the aging process at the skin and bone levels, respectively. Both conditions are associated with increased morbidity for elderly people, and this requires necessary interventions. They share many common risk factors; among these, vitamin D (VD) deficiency appears to have a role. VD is involved in either disease with many mechanisms, among which immunomodulation. VD deficiency has been linked to OP because it inhibits the body's capacity to absorb calcium and maintain optimal bone health. Available evidence suggests that proper vitaminosis D also appears to be vital in preventing skin age-related issues. DP is often seen in elderly individuals, particularly those with long-term sun exposure and a history of chronic sun damage. VD deficiency can be linked to DP, since its involvement in collagen production, epidermal barrier function, inflammation regulation, wound healing, and sun protection. Aim of this review is to summarize the most updated existing evidence on the role of VD in the development of fragility syndromes such as DP and OP and the possible benefits of VD supplementation as a simple and harmful weapon against aging.

Long-Term Safety of Growth Hormone Deficiency Treatment in Cancer and Sellar Tumors Adult Survivors: Is There a Role of GH Therapy on the Neoplastic Risk?

Experimental studies support the hypothesis that GH/IGF-1 status may influence neoplastic tissue growth. Epidemiological studies suggest a link between GH/IGF-1 status and cancer risk. However, several studies regarding GH replacement safety in childhood cancer survivors do not show a prevalence excess of de novo cancers, and several reports on children and adults treated with GH have not shown an increase in observed cancer risk in these patients. The aim of this review is to provide an at-a-glance overview and the state of the art of long-term effects of GH replacement on neoplastic risk in adults with growth hormone deficiency who have survived cancer and sellar tumors.

Craniopharyngioma and Metabolic Syndrome: A 5-Year Follow-Up Single-Center Experience.

Patients with craniopharyngioma often have comorbidities, such as obesity and hypopituitarism. These two conditions affect each other and worsen the quality of life of patients, which lead to a higher risk of morbidity and mortality. In addition, abdominal obesity, measured as waist circumference (WC), is together with other parameters [arterial hypertension, hyperglycemia, hypertriglyceridemia, and reduced levels of high-density lipoprotein (HDL) cholesterol], one of the components of metabolic syndrome (MS). Each one of these morbidities occurs in patients with craniopharyngioma more frequently than in the remaining population. On these bases, we evaluated metabolic parameters in patients with craniopharyngioma at the time of diagnosis and after a 5-year follow-up, which compares these data with those of age-, gender-, WC-, and body mass index (BMI)-matched controls. In addition, we evaluated the prevalence of MS according to IDF criteria (MS-IDF) and the prevalence of MS according to ATP III (MS-ATPIII) criteria in patients and controls at baseline and after 5 years. We recruited 20 patients with craniopharyngioma (age 38.5 ± 15 years, 10 M) and 20 age-, gender-, WC- and BMI-matched controls (age 34.16 ± 13.19 years, 10 M). In all patients and controls, we evaluated the following: anthropometric features [height, weight, BMI, WC, hip circumference (HC) and waist-to-hip ratio (WHR)], systolic blood pressure (SBP) and diastolic blood pressure (DBP), lipid profile [total cholesterol (TC), HDL, low-density lipoprotein (LDL) cholesterol, triglycerides (TG)], and blood glucose at baseline and after 5 years. The prevalence of MS, according to IDF and ATPIII criteria, was calculated in the two groups at baseline and after 5 years. According to our results, at baseline, patients with craniopharyngioma had a worse metabolic profile than controls and a higher prevalence of MS. Besides, at a 5-year follow-up, patients still had impaired metabolic characteristics and more frequent MS (according to IDF and ATPIII criteria) when compared to controls. These data confirm that MS in patients with craniopharyngioma is unresponsive to life-changing interventions and to a common pharmacological approach. Other factors may be involved in the evolution of these conditions; so, further studies are needed to establish the correct management of these patients.

Vitamin D deficiency: a potential risk factor for cancer in obesity?

Obesity is considered an abnormal or excessive accumulation of adipose tissue, due to a prolonged positive energy balance that arises when energy intake is greater than energy expenditure, leading to an increased risk for the individual health and for the development of metabolic chronic diseases including several different types of cancer. Vitamin D deficiency is a metabolic alteration, which is often associated with the obesity condition. Vitamin D is a liposoluble vitamin, which plays a pivotal role in calcium-phosphate metabolism but extraskeletal effects have also been described. Among these, it plays an important role also in adipocyte physiology and glucose metabolism, typically dysregulated in subjects affected by obesity. Moreover, it is now recognized that Vitamin D also influences the processes of cell proliferation, differentiation, adhesion potentially leading to carcinogenesis. Indeed, data indicate a potential link between vitamin D levels and cancer, and higher vitamin D concentrations have been associated with a lower risk of developing different kinds of tumors, including breast, colon, lymphoma, lung, and prostate cancers. Thus, this review will revise the literature regarding this issue investigating and highlighting the potential mechanism of action, which might lead to new therapeutical options.

Multidisciplinary management of osteoporotic vertebral fractures.

Vertebral fractures represent the most frequent complication associated with osteoporosis. Patients harboring a vertebral fracture complain physical impairment including low back pain and spine balance alteration, i.e., kyphosis, leading to subsequent systemic complication, with an increase in morbidity and mortality risk. Different strategies are available in the management of osteoporotic vertebral fractures: medical therapy acts as a prevention strategy while surgical vertebral augmentation procedures, when correctly indicated, aim to reduce pain and to restore the physiological vertebral height. Considering the growing prevalence and incidence of this condition and its socio-economic burden, prevention, diagnosis and treatment of osteoporotic vertebral fractures are of utmost importance. Our aim is to review the current strategies for the management of osteoporotic vertebral fractures providing an integrated multidisciplinary endocrinological, radiological and neurosurgical point of view.

Craniopharyngioma, Chronotypes and Metabolic Risk Profile.

AIM: To investigate the potential association among Craniopharyngioma (CP), chronotypes and metabolic risk profile. SUBJECTS AND METHODS: The study population included 28 patients (46.4% males; 42.6 ± 15.8 years) and 28 controls, age, gender and BMI matched (46.4% males; 46.5 ± 12.9 years). In this study sample, we evaluated: anthropometric measurements (waist circumference, WC; BMI), plasma glucose, lipid profile, and systolic (SBP) and diastolic (DBP) blood pressure. Morningness-Eveningness was measured with the Horne-Ostberg Morningness-Eveningness Questionnaire (MEQ), which included 19 questions about preferred sleep time and daily performance. RESULTS: in both patients and controls grade I obesity was detected in 15 subjects (53.6%), grade II obesity in 13 subjects (46.4%). In the patient group, the mean score of chronotype was 47.8 ± 12.6. In particular, 9 patients (32.1%) exhibited the morning chronotype, 6 (21.4%) the intermediate chronotype and 13 (46.4.%) the evening chronotype. No significant difference was found in gender and age among the chronotype categories. Patients with the evening chronotype had higher blood pressure values and worse metabolic parameters than those with the morning chronotype. In the control group, the mean score of the chronotype was 57.6 ± 9.5. In particular, 16 (57.1%) subjects exhibited the morning chronotype, 10 (35.7%) the intermediate chronotype and only 2 (7.1.%) the evening chronotype. The prevalence of intermediate and evening chronotypes was higher in females than males (p = 0.021), while males have a higher prevalence of the morning chronotype. Subjects with intermediate and evening chronotypes had worse metabolic parameters than those with the morning chronotype. In patients, the chronotype score was inversely correlated to WC, BMI, SBP, DBP, plasma glucose, total cholesterol, triglycerides, LDL cholesterol and positively correlated with HDL cholesterol. No correlation was found between age and chronotype. In controls, the chronotype score was inversely correlated to WC, BMI, plasma glucose, total cholesterol, LDL cholesterol. No correlation was found among chronotype and age, blood pressure, triglycerides, HDL cholesterol. Considering the whole population of the study (patients and controls), at logistic regression the chronotype score was significantly associated with the presence of CP. CONCLUSIONS: for the first time thus far, our study puts the light on the association of the CP with chronotypes and metabolic alterations in this disease, which are the main determinants of the reduced quality of life, higher morbidity and mortality in this setting of patients. This finding suggests that alterations of chronotype might represent an adjunctive risk for CP patients and a possible target for their integrate management.

Impact of Long-Term Growth Hormone Replacement Therapy on Metabolic and Cardiovascular Parameters in Adult Growth Hormone Deficiency: Comparison Between Adult and Elderly Patients.

Growth hormone deficiency (GHD) in adults is due to a reduced growth hormone (GH) secretion by the anterior pituitary gland which leads to a well-known syndrome characterized by decreased cognitive function and quality of life (QoL), decreased bone mineral density (BMD), increased central adiposity with a reduction in lean body mass, decreased exercise tolerance, hyperlipidemia and increased predisposition to atherogenesis. Considering some similar features between aging and GHD, it was thought that the relative GH insufficiency of the elderly person could make an important contribution to the fragility of elderly. GH stimulation tests are able to differentiate GHD in elderly patients (EGHD) from the physiological reduction of GH secretion that occurs with aging. Although there is no evidence that rhGH replacement therapy increases the risk of developing Diabetes Mellitus (DM), reducing insulin sensitivity and inducing cardiac hypertrophy, long-term monitoring is, however, also mandatory in terms of glucose metabolism and cardiovascular measurements. In our experience comparing the impact of seven years of rhGH treatment on metabolic and cardiovascular parameters in GHD patients divided in two groups [adult (AGHD) and elderly (EGHD) GHD patients], effects on body composition are evident especially in AGHD, but not in EGHD patients. The improvements in lipid profile were sustained in all groups of patients, and they had a lower prevalence of dyslipidemia than the general population. The effects on glucose metabolism were conflicting, but approximately unchanged. The risk of DM type 2 is, however, probably increased in obese GHD adults with impaired glucose homeostasis at baseline, but the prevalence of DM in GHD is like that of the general population. The increases in glucose levels, BMI, and SBP in GHD negatively affected the prevalence of Metabolic Syndrome (MS) in the long term, especially in AGHD patients. Our results are in accordance to other long-term studies in which the effects on body composition and lipid profile are prominent.

Treatment of Paget's disease of the bone: long-term effect of neridronate in a real-life setting.

BACKGROUND: Bisphosphonates represent the gold standard treatment for Paget's disease of bone. Neridronate is a potent bisphosphonate, licensed in Italy for this use, but only few clinical trials have investigated the outcomes of this treatment. The aim of our study was to report our long-term experience with intravenous Neridronate. METHODS: This is a 48 months observational, descriptive and prospective study on patients with active Paget's disease of bone treated with intravenous Neridronate. Patients underwent laboratory tests (total alkaline phosphatase (ALP), calcium, phosphate, 25 OH Hydroxivitamin D, serum protein electrophoresis, parathyroid hormone) at the time of diagnosis and every 6 months. In all subjects, mutations in the SQSTM1 and ZNF687 genes were searched. The primary endpoint was the treatment efficacy in term of rate of therapeutic response at 48 months (normalization of ALP levels or a reduction of at least 75% in total ALP excess). RESULTS: Fifteen patients (10 female, mean age 70.3 years) were enrolled at our division from 2016 to 2020. One was positive for the ZNF687 gene mutation. After 48-month follow-up, the therapeutic response was maintained in 80% of patients treated with intravenous neridronate. ALP values were higher at 48 months than at 6 months, but this difference was not clinically relevant because the percentage of subjects who maintained a therapeutic response at 48 months was not significantly different from that observed at 6 months (80% vs. 86.6%, P=0.62). One patient had a biochemical relapse, and was retreated with the same therapeutic regimen, achieving a good response. CONCLUSIONS: Treatment with intravenous neridronate is effective in inducing and maintaining sustained remission in patients with PDB for at least 48 months. Administration in single intravenous infusion may improve long-term compliance compared to oral formulations.

Vitamin D and Sleep Regulation: Is there a Role for Vitamin D?

BACKGROUND: Vitamin D exerts multiple pleiotropic effects beyond its role in calcium-phosphate metabolism. Growing evidence suggests an association between hypovitaminosis D and sleep disorders, thus increasing the interest in the role of this vitamin in the regulatory mechanisms of the sleep-wake cycle. OBJECTIVE: The study aimed to explore and summarize the current knowledge about the role of vitamin D in sleep regulation and the impact of vitamin D deficiency on sleep disorders. METHODS: The main regulatory mechanisms of vitamin D on sleep are explained in this study. The literature was scanned to identify clinical trials and correlation studies showing an association between vitamin D deficiency and sleep disorders. RESULTS: Vitamin D receptors and the enzymes that control their activation and degradation are expressed in several areas of the brain involved in sleep regulation. Vitamin D is also involved in the pathways of production of Melatonin, the hormone involved in the regulation of human circadian rhythms and sleep. Furthermore, vitamin D can affect sleep indirectly through non-specific pain disorders, correlated with alterations in sleep quality, such as restless legs syndrome and obstructive sleep apnea syndrome. CONCLUSION: Vitamin D has both a direct and an indirect role in the regulation of sleep. Although vitamin D deficiency has been associated to sleep disorders, there is still scant evidence to concretely support the role of vitamin D supplementation in the prevention or treatment of sleep disturbances; indeed, more intervention studies are needed to better clarify these aspects.

Clinical outcome in differentiated thyroid carcinoma and microcarcinoma.

INTRODUCTION: Due to the frequent use of neck ultrasonography, the incidence of differentiated thyroid microcarcinoma (DTMC), defined as a lesion with greatest dimension ≤1 cm, is increasing worldwide. Although DTMC generally has a lower aggressivity and a better prognosis than differentiated thyroid carcinoma (DTC), some cases of clinically aggressive DTMC were found. The aim of this study is to compare the rate of recurrence in DTMC and DTC, during a 3-year follow-up. METHODS: Patients with differentiated thyroid carcinoma, who underwent total thyroidectomy and postoperative (131)I-RAI ablation, were stratified according to lesion diameter (DTC for diameter > 1 cm or DTMC ≤ 1 cm). After surgery, patients underwent a 3-year follow-up. Recurrent disease was defined on the basis of positive biochemical (Tg > 2 ng/ml under TSH-suppression or after rhTSH-stimulation) and/or imaging (US, WBS, CT, PET/CT) findings. RESULTS: 449 patients have been included in the final analysis. Linfoadenectomy rate and RAI ablative dose were significantly higher in DTC than in DTMC (32.7% vs. 22.4%, p = 0.018 and 112.3 ± 21 vs. 68.3 ± 24.1 mCi, p < 0.001). During the follow-up, 50 carcinoma recurrences occurred, more frequent in DTC than in DTMC (15.6% vs. 7.6%, p = 0.010). After adjustment for gender, age, rate of lymph node dissection and 131I dose of RAI treatment, the difference in the risk of recurrence was no longer significant among DTC and DTMC patients (HR: 1.585, 95% CI 0874-2877, p = 0.130). CONCLUSIONS: The prediction of disease severity cannot be based exclusively on lesion diameter. A more careful therapeutic approach and follow-up should be recommended in DTMC patients.