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BackgroundGrowing evidence reveals the important role of clinical psychological factors in chronic-immune diseases. The aim of this study was to investigate Health-Related Quality of Life (HR-QoL), depression, anxiety, and alexithymia in patients with severe hypersensitivity reactions such as Severe Allergic Asthma (SAA) and Hymenoptera Venom Anaphylaxis (HVA).MethodsThe Short-Form Health Survey-36 (SF-36), the Beck Depression Inventory Questionnaire (BDI-II), the Hamilton Anxiety Rating Scale (HAM-A) and the Toronto Alexithymia Scale (TAS-20) were used to assess HR-QoL and clinical psychological features of patients with SAA and HVA.ResultsOverall, 78 patients were recruited. Patients with SAA (n = 35) reported lower scores for physical functioning [65 (58–75) vs. 90 (85–95); p =

A comprehensive investigation of psychological features in chronic patients is very important for tailoring effective treatments. In this study we tested anxiety, depression, health related quality of life (HR-QoL), alexithymia, coping styles, and defense mechanisms, in eighty-four patients with Crohn disease (CD) and ulcerative colitis (UC). Participants reported low to moderate HRQoL and anxiety, apart from alexithymia. Women experienced lower QoL and higher levels of anxiety and depressive symptoms. Coping and defense strategies were related to distress symptoms and QoL. Positive attitude and principalization, showed negative associations with depression, anxiety and alexithymia and were also found to be associated with mental health. CD patients used significantly more turning against objects (p=0.02) and projections (p=0.01) and UC patients used more reversal (p=0.04). Elderly women showed higher anxiety symptoms and lower perceived QoL. Multiple regression analysis revealed anxiety and depression were independently associated with QoL. Significant differences emerged in defense styles among CD and UC. CD participants used more maladaptive coping and defense styles which were related to mental distress, depression and anxiety, together with higher level of alexithymia. Findings suggest that psychological aspects play a key role in mental health in patients suffering from inflammatory bowel diseases. A multi-integrated clinical strategy including psychotherapeutic interventions should be considered in treating CD and UC.

Growing evidence from scientific research elucidates the important role of alexithymia in chronic immune diseases. This Review aims to explore the presence of alexithymia in patients affected by asthma and clarify its associations with other involved psychological and physical factors. In January 2023, according to PRISMA guidelines, a systematic search using PubMed and Scopus was conducted. Twenty-six studies were eligible based on inclusion criteria. Alexithymia was significantly present in asthma patients, with most studies reporting a higher prevalence (from 9 to 62.8%) than in control groups (approximately 10%). The coexistence of asthma and alexithymia was associated with a worse quality of life, psychiatric comorbidity, poor symptom control, and difficulty in recognizing exacerbations of the disease. These results suggest that alexithymia can negatively impact the management of asthma. For this reason, we recommend an accuracy assessment in clinical settings and the implementation of psychological interventions to promote the emotional and physical wellbeing of asthmatic patients.

Glucocorticoid-induced osteoporosis (GIO) complicates the clinical management of patients subjected to long-term glucocorticoid use. This study explored the effects of genistein on bone loss in a randomized double-blind alendronate-controlled trial in postmenopausal women with GIO. 200 postmenopausal women (taking at least 5 mg of prednisone equivalents) since 3 months, or more, and expected to continue for at least other 12 months, were randomized to receive genistein (54 mg/day daily) or alendronate (70 mg once a week) for 24 months. Both groups received also Calcium and Vitamin D3 supplementation. Median bone mineral density (BMD) at the antero-posterior lumbar spine significantly increased from 0.75 g/cm2 at baseline to 0.77 g/cm2 at 1 year and 0.79 g/cm2 at 2 years in alendronate-treated patients and from 0.77 g/cm2 at baseline to 0.79 g/cm2 at 12 months and to 0.80 g/cm2 at 24 months in genistein recipients. No difference was observed between the two treatments. Median BMD at the femoral neck increased from 0.67 g/cm2 at baseline to 0.68 g/cm2 at 1 year and 0.69 g/cm2 at 2 years in alendronate-treated patients and from 0.68 g/cm2 at baseline to 0.70 g/cm2 at 12 months and to 0.71 g/cm2 at 24 months in genistein recipients. No difference was observed between alendronate and genistein groups in BMD. Regarding bone markers genistein and alendronate statistically decreased c-terminal telopeptide, while osteocalcin, bone-ALP, and sclerostin showed greater changes in genistein treated patients. This randomized clinical trial suggests that genistein aglycone represents an additional therapeutic option for patients with GIO.

IntroductionPsychological features have been bidirectionally associated with osteoporosis, but it is still unclear whether patient’s anxiety fluctuations during the anti-osteoporotic treatment can have an impact on bone mineral density (BMD) variation. The aim of this study was to investigate the interrelations between psychological distress features, such as anxiety, depression, health-related QoL (HRQoL) and bone health in women receiving anti-osteoporotic treatment.Methods192 post-menopausal osteoporotic women were treated with alendronate or risedronate according to the standard procedure. The levels of anxiety, depression, and perceived HRQoL, along with BMD, were assessed at baseline and at a 2-year follow-up.ResultsAt the end of the study, the patients showed a statistically significant increase of both psychic and somatic anxiety (p

There is growing interest in the relationship between chronic kidney disease (CKD) and fragility fracture risk. Bone mineral density (BMD) is a major determinant of bone strength, although its role as a predictor of fracture in advanced CKD and hemodialysis is still under debate. We aimed to further investigate surrogates of bone quality and their associations with muscle strength and fracture risk in hemodialysis. Multiple clinical risk factors for fracture and an estimated 10-year probability of fracture, BMD at lumbar spine and femur, trabecular bone score (TBS), X-ray vertebral morphometry, phalangeal bone quantitative ultrasonography (QUS), tibial pulse-echo ultrasonography (PEUS), and handgrip strength were evaluated in a setting of hemodialysis patients in treatment with acetate-free biofiltration (AFB) or bicarbonate hemodialysis. The bone ultrasound measurements, both at phalangeal and tibial sites, were significantly associated with lumbar and femoral DXA values. Handgrip strength was significantly associated with the 10-year probability of fracture (r = −0.57, p < 0.001 for major fractures and r = −0.53, p < 0.001 for hip fracture, respectively), with femur neck, total femur, and L1–L4 BMD values (r = 0.47, p = 0.04; r = 0.48, p = 0.02; r = 0.58, p = 0.007, respectively), with TBS at the lumbar spine (r = 0.71, p < 0.001) and with the phalangeal QUS measure of AD-SoS (r = 0.369, p = 0.023). In the hemodialysis group, 10 participants (24.3%) reported at least one morphometric vertebral fracture (Vfx); conversely, only six participants (15%) showed Vfx in the control group. In the hemodialysis group, participants with Vfx compared with participants without Vfx reported significantly different TBS, bone transmission time (BTT), cortical thickness, and handgrip strength (p < 0.05). At multiple regression analysis, by identifying as dependent variable the 10-year fracture risk for major fracture, after correcting for age, BMI, time since dialysis, AD-SoS, cortical bone thickness, and handgrip strength, only BTT (β = −15.21, SE = 5.91, p = 0.02) and TBS (β = −54.69, SE = 21.88, p = 0.02) turned out as independently associated with fracture risk. In conclusion, hemodialysis patients showed a higher fracture risk and lower surrogate indices of bone strength as TBS and QUS parameters. In this cohort of patients, handgrip strength measurements appeared to be a useful instrument to identify high-fracture-risk subjects.

Cadmium (Cd) represents a public health risk due to its non-biodegradability and long biological half-life. The main target of Cd is the kidney, where it accumulates. In the present narrative review, we assessed experimental and clinical data dealing with the mechanisms of kidney morphological and functional damage caused by Cd and the state of the art about possible therapeutic managements. Intriguingly, skeleton fragility related to Cd exposure has been demonstrated to be induced both by a direct Cd toxic effect on bone mineralization and by renal failure. Our team and other research groups studied the possible pathophysiological molecular pathways induced by Cd, such as lipid peroxidation, inflammation, programmed cell death, and hormonal kidney discrepancy, that, through further molecular crosstalk, trigger serious glomerular and tubular injury, leading to chronic kidney disease (CKD). Moreover, CKD is associated with the presence of dysbiosis, and the results of recent studies have confirmed the altered composition and functions of the gut microbial communities in CKD. Therefore, as recent knowledge demonstrates a strong connection between diet, food components, and CKD management, and also taking into account that gut microbiota are very sensitive to these biological factors and environmental pollutants, nutraceuticals, mainly present in foods typical of the Mediterranean diet, can be considered a safe therapeutic strategy in Cd-induced kidney damage and, accordingly, could help in the prevention and treatment of CKD.

Haemophilia A (HA) and haemophilia B (HB) are X-linked inherited bleeding disorders caused by the absence or deficiency of coagulation factors VIII (FVIII) and IX (FIX), respectively. Recent advances in the development of effective treatments for haemophilia have led to a significant increase in life expectancy. As a result, the incidence of some comorbidities, including fragility fractures, has increased in people with haemophilia (PWH). The aim of our research was to perform a review of the literature investigating the pathogenesis and multidisciplinary management of fractures in PWH. The PubMed, Scopus and Cochrane Library databases were searched to identify original research articles, meta-analyses, and scientific reviews on fragility fractures in PWH. The mechanism underlying bone loss in PWH is multifactorial and includes recurrent joint bleeding, reduced physical activity with consequent reduction in mechanical load, nutritional deficiencies (particularly vitamin D), and FVIII and FIX deficiency. Pharmacological treatment of fractures in PWH includes antiresorptive, anabolic and dual action drugs. When conservative management is not possible, surgery is the preferred option, particularly in severe arthropathy, and rehabilitation is a key component in restoring function and maintaining mobility. Appropriate multidisciplinary fracture management and an adapted and tailored rehabilitation pathway are essential to improve the quality of life of PWH and prevent long-term complications. Further clinical trials are needed to improve the management of fractures in PWH.

Abstract Osteopoikilosis (OP) is a rare autosomal dominant sclerosing bone disease, caused by heterozygous mutations in the LEMD3 gene. It is characterised by numerous focal lamellar bone compact deposits in the spongiosa. In this case report, we describe a famliar case of OP and review the literature.

Zoledronic acid (Zol) is a widely used intravenous aminobisphosphonate to treat both benign and malignant skeletal diseases, and bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious side effect whose pathophysiology remains poorly understood. Vascular Endothelial Growth Factor (VEGF) has been recognized to mediate BRONJ in cancer patients undergoing Zol treatment, however data on VEGF are lacking in patients with osteoporosis. Increasing evidences demonstrate that vitamin D influences VEGF levels. The aim of this study was to investigate the influence of Zol on VEGF levels and the possible role for vitamin D on the Zol mediated changes of VEGF concentration in women with postmenopausal osteoporosis. Twenty-eight postmenopausal women with osteoporosis were enrolled and randomized into two groups to receive Zol (5 mg) or placebo. At baseline, at day-3 and day-30 VEGF serum levels were measured; bone turnover markers, 25-hydroxyvitamin D [25(OH)D] and serum calcium were evaluated at baseline. In Zol-treated women, VEGF increased significantly on day-3, and then decreased on day-30. In the Zol-treated women, the percent change of VEGF levels between baseline and day-30 (−18% at day-30 vs. baseline, p = 0.01) was significantly associated with serum 25(OH)D values (r = 0.29, p = 0.028). At a stepwise multiple regression analysis, after correcting for age, BMI, time since menopause, femoral neck BMD, osteocalcin, C-terminal telopeptide of type 1 collagen, and baseline VEGF levels, 25(OH)D levels were independently associated with VEGF change (β = 1.7, SE = 0.71, p = 0.03). For the first time, we detected early modifications of circulating VEGF in postmenopausal women receiving Zol for osteoporosis, identifying a vitamin D-dependent modulation of these changes.

Due to increasing life expectancy in thalassemia major (TM), osteoporosis is emerging as a significant problem. Its aetiology is multifactorial, culminating in increased bone resorption and impaired remodelling. Hypogonadism and marrow expansion seem to play an important role, but iron overload, deferoxamine toxicity, a defective growth hormone-insulin-like growth factor-1 axis and multiple endocrinopathies may represent additional causes of bone damage. Many of these patients, though under appropriate treatment programs, do not achieve normal peak bone mass. The receptor activator of nuclear factor kappa-ß (RANK)/RANK ligand/osteoprotegerin and the Wnt/β-catenin systems work as major mediators of imbalanced bone turnover and bone loss. Additional genetic factors, such as collagen type 1 alpha 1 and vitamin D receptor gene polymorphisms, may exert some influence on the enhanced fracture risk observed in TM. To date, in spite of adequate hormone replacement, chelating therapy and acceptable haemoglobin levels, subjects with TM display impaired bone density and imbalanced bone turnover, thus the puzzle of the pathogenesis of TM-induced osteoporosis remains far from being solved.

Background: This systematic review analyzed the relationship between alexithymia, considered as the inability to recognize and express thoughts and emotions, and type 2 diabetes mellitus (T2DM), one of the most common chronic illness, characterized by a metabolic disorder burdened by high morbidity and mortality worldwide due to its outcomes.Methods: PRISMA guidelines were followed throughout this systematic review of the recent literature indexed in the databases PubMed, PsycInfo, Scopus, and Web of Science. Search terms for eligible studies were: “Type 2 diabetes” OR “T2DM” AND “Toronto Alexithymia Scale” OR “TAS-20”[All Fields].Results: The initial search identified 61 indexed scientific publications. After screening we found that seven publications met the established scientific inclusion and exclusion criteria. It emerged that alexithymic patients ranged from 25 to 50% across the examined publications and it appeared that patients with T2DM generally reflected greater values of alexithymia, revealing particular differences among TAS domains. Moreover, emlpoyed participants were alexithymic to a greater extent compared to non-working participants (77.8 vs. 35.4%) and alexithymia was 2.63 times more severe among working participants when examining predictors of alexithymia. When evaluating the correlations between alexithymia and HbA1c or fasting blood glucose levels we found strong associations equal to 0.75 and 0.77 for TAS-20 total scores, respectively. While alexithymic participants showed significantly higher levels of HbA1c and blood glucose when compared to the non-alexithymic participants.Conclusions: The results of this systematic review of the current literature highlight the need of alexithymia evaluation in patients with T2DM. The high prevalence in T2DM and strong associations with poorly regulated diabetes and psychological distress, indicate a significant relationship between poor glycemic control and psychological distress, such as anxiety and depression, and quality of life. Further studies are needed focusing on age and gender differences in order to be able to improve clinical psychological care and prevention.

IntroductionAromatase inhibitors (AIs) dramatically increased breast cancer (BC) survival, leading to enhanced attention to their long-term consequences on psychological functioning. Conflicting data has been examined regarding the association between AIs administration and the clinical psychological features in BC survivors (BCSs).PurposeAs psychological symptoms often occur in such chronic diseases, our study aimed at exploring anxious and depressive symptoms and the perceived quality of life (QoL) in BCSs assessed for osteoporosis.MethodsThe total sample consisted of a clinical sample of 51 outpatient postmenopausal women, diagnosed with BC, and a control group composed of 51 healthy postmenopausal women. All recruited participants were evaluated through the clinical gold standard interview and completed the following self-rating scales: the Hamilton Anxiety Rating Scale, Beck Depression Inventory II edition, and 36-Item Short Form Health Survey, which were administered at baseline and after 6 months in BCSs in AIs treatment, compared with controls. Moreover, all participants were assessed for vitamin D status, bone mineral density (BMD) and subclinical vertebral fractures. Data regarding age, age at menopause, body mass index (BMI), smoking habits and alcohol consumption was collected.ResultsBCSs (n = 51) showed higher anxious and depressive symptoms, and lower perceived QoL vs. controls (n = 51) (pConclusionsThe improvement of clinical psychological features and perceived QoL was associated with AIs treatment in women being treated with, for early breast cancer. Further studies are needed to obtain a deeper comprehension of the correlation between clinical psychological and physical features in BCSs.

Backgrounds: Psychological factors may affect patients’ ability to cope with chronic illness, which occur with a high incidence as they represent age related disorder. Anxiety, depression and alexithymia could specifically interfere with compliance and adherence leading to predictable consequences and predicting morbidity and mortality independently of several confounders. The present work aims at investigating the relationship between alexithymia and affective dimension such as anxiety and depression levels, and health related quality of life in T2DM patients. Particularly, alexithymia was analyzed in its three main facets and time since diagnosis was considered with also metabolic control. Methods: Forty seven patients with T2DM were consecutively enrolled and assessed with a gold standard interview and with a psycho-diagnostic evaluation. Clinical psychological exploration consisted of HAM-A, BECK-II, SF-36 and TAS-20 administration. Statistical analysis was performed using IBM SPSS statistical version 25. Data were analyzed anonymously. Results: 47 participants showed moderate depressive symptoms as confirmed by the mean BDI-II and HAMA-A score (15.14 ± 8.95 and 24.31 ± 6.95, respectively), suggesting a high prevalence of anxiety in the enrolled subjects. It was observed a lower perceived QoL as resulted by the MCS and PCS mean values (37.68 ± 9.41 and 39.31 ± 12.29, respectively) and TAS-20 highlighted considerable mean values of 60.53 ± 7.93 in the recruited participants with a prevalence in EOT values (27.51± 4.27), in comparison with mean DID and DDF values (17.26 ± 5.52 and 15.48 ± 3.84, respectively). Conclusions: Our study may suggest a predictive role of alexithymia in patients with T2DM. Moreover, lower PCS and MCS, revealing worst perceived QoL were associated to both higher anxiety and disease duration.

The study aimed to investigate cross-sectionally the associations of cognitive reserve (CR) and premorbid IQ with cognitive and functional status in a cohort of older outpatients. Additionally, we evaluated the association of CR and premorbid IQ with the worsening of patients’ cognitive status at one-year follow-up. We originally included 141 outpatients (mean age 80.31 years); a telephone-based cognitive follow-up was carried out after one year, including 104 subjects (mean age 80.26 years). CR (β = 0.418), premorbid IQ (β = 0.271) and handgrip strength (β = 0.287) were significantly associated with the MMSE score. The cognitive worsening at follow-up was associated with lower CR, lower MMSE score, reduced gait speed and frailty exhibited at baseline. Univariate linear regressions showed that CR was associated with handgrip strength (β = 0.346), gait speed (β = 0.185), autonomy in basic (β = 0.221) and instrumental (β = 0.272) daily activities, and frailty (β = −0.290); premorbid IQ was significantly associated with autonomy in instrumental daily activities (β = 0.211). These findings highlight the need for integrating CR and premorbid IQ with physical and motor measures when appraising predictors of cognitive decline in the elderly population. The study also newly extends the link of CR and premorbid IQ to the functional status in older adults.

Background: It is known that cognitive impairment is associated with low bone mineral density (BMD) and that low BMD is also observed in elderly people with neurodegenerative diseases, in which executive functions (EF) could be decreased. A limited number of studies investigated the association between EF with BMD and fracture risk in elderly women. Aims: The aim of this study was to explore the association between cognitive impulsivity, BMD and fall risk in a sample of postmenopausal women evaluated for osteoporosis. Methods: We consecutively recruited women who obtained a score ≥ 24 at the Mini Mental State Examination (MMSE). Cognitive impulsivity was evaluated by the Stroop Colour and Word Test (SCWT). BMD was detected by dual-energy X-ray absorptiometry at lumbar spine and femoral neck. Results: Cognitive impulsivity, as evidenced by the greater number of errors at the SCWT, was significantly related with BMD values at lumbar spine and femoral neck (r= -0.39, p= 0.01 and r= -0.43, p= 0.008; respectively), suggesting a neuropsychological impairment in patients assessed for osteoporosis. Moreover, interference effect on response time was significantly associated with higher prevalence of falls (r= 0.342; p= 0.031). Discussion and Conclusions: Our findings suggested a potential involvement of cognitive impulsivity on BMD and risk of fall. This is a relevant issue in clinical practice for both clinical psychologists and physicians who evaluate postmenopausal women, to eventually predict risk of fracture.

IntroductionAge-related medical conditions are increasing worldwide. Type 2 Diabetes mellitus (T2DM) represents a chronic disease, which affects a large amount of general population, accounting for over 90% of diabetes mellitus (DM) cases.PurposeAs psychopathological symptoms frequently occur in medical conditions, our study aimed at exploring whether psychological factors and metabolic control may affect health related quality of life (HRQoL).MethodsForty five patients with T2DM were consecutively recruited and assessed with a psychodiagnostic battery: Hamilton Anxiety Rating Scale (HAM-A), Beck Depression Inventory II edition (BDI-II) and the 36-Item Short Form Health Survey (SF-36), including indexes Physical and Mental Component Summary (PCS, MCS). Moreover, time since DM diagnosis and glycated hemoglobin (HbA1c) values were detected.ResultsParticipants (mean age 65.3 ± 5.9 years) had a mean time since diagnosis of 11.6 ± 6.7 years, and showed a good metabolic control as highlighted by mean HbA1c values 7.1 ± 0.9%. Median HAM-A score [25(20.7–30.6)], represented high prevalence of anxious symptoms. A moderate expression of depressive symptoms was observed [BDI-II score: 13(8.3–21.4)]. A multiple regression analysis, after correcting for age, BMI, HbA1c value and BDI-II score, showed the perceived quality of life relative to PCS was significantly related to both disease duration (β = −0.55, p = 0.03, SE = 0.25) and HAM-A scores (β = −0.52, p = 0.04, SE = 0.24). Moreover, both HAM-A (β = −0.67, p = 0.01, SE = 0.26) and BDI-II (β = −0.48, p = 0.02, SE = 0.20) scores were independently predictive of MCS. Metabolic control, instead, was not a significant predictor.ConclusionOur study suggests a predictive role of both anxiety levels and time since diagnosis in perceived HRQoL in T2DM patients. PCS was associated with anxiety and time since diagnosis and MCS was associated with anxiety and depressive symptoms but not with diabetes duration or metabolic control. These data could be useful to plan T2DM training programs focused on psychological health concerns, possibly leading to a healthy self-management and a better perceived HRQoL, even assisting patients in reducing the negative effect due to the chronicization of T2DM.

Objective: Cross-sectional studies have reported that TSH above or close to the upper normal limit correlates with unfavorable metabolic and cardiovascular outcomes. Certain medications impair intestinal absorption of levothyroxine (L-T4), resulting in undertreated hypothyroidism (viz. failure of serum TSH to reach target levels, if hypothyroidism is primary).Further to evaluating the magnitude of sub-optimally treated primary hypothyroidism as a result of co-ingestion of those medications, we wished to ascertain whether the above complications would occur during a low number of years under polypharmacy. Method: In this retrospective study in collaboration with 8 family physicians, we enrolled adults with primary hypothyroidism under L-T4 therapy that, for 2 years minimum, was not associated with those medications (non-exposure, baseline) and that, for another 2 years minimum, it was (exposure). Outcomes were serum levels and proportions of serum TSH levels >4.12 mU/L, and proportions of complications. Complications were aggravation of pre-existing or de novo onset of any of metabolic syndrome, impaired fasting glycemia (IFG), diabetes mellitus, dyslipidemia, hypertension, coronary heart disease (CHD), cerebrovascular disease (CVD). Result: A total of 114 patients were enrolled. Duration of exposure to the interfering medication was 32.1 ± 6.9 months (median 31; range 24–55). Compared with non-exposure, the exposure period resulted in greater TSH levels (2.81 ± 3.62 [median 1.79] vs 1.27 ± 1.34 [median 0.93], P = 2.2 × 10−20) and proportions of values >4.12 mU/L (18.5% vs 4.7%, P = 1.2 × 10−7). Seventy-six patients (67%) had complications, whose rates of TSH >4.12 mU/L were greater than in the 36 complication-free patients (22% vs 11%, P = 0.018). Conclusion: During a median period of 31 months, there are relevant consequences for L-T4 treated adult hypothyroid patients resulting from hyperthyrotropinemia caused by medications impairing L-T4 absorption. This should be taken into account by future guidelines on hypothyroidism management. Keywords: Subclinical hypothyroidism, Levothyroxine malabsorption, Diabetes mellitus, Dyslipidemia, Hypertension, Cardiovascular diseases

Vitamin D modulates bisphosphonate (BP) efficacy, but its contribution to bone mineral density (BMD) after BP discontinuation is not known. To address this topic, we performed a retrospective analysis of postmenopausal women exposed to alendronate (ALN) to treat osteoporosis who regularly continued the supplementation of cholecalciferol or calcifediol at recommended doses. In the ninety-six recruited women (age 61.1 ± 6.9 years), ALN was administered for 31.2 ± 20.6 months and then discontinued for 33.3 ± 18.9 months. The modification of 25(OH)D serum levels over time was associated with a change of alkaline phosphatase (r = −0.22, p = 0.018) and C-terminal collagen type 1 telopeptide (r = −0.3, p = 0.06). Women in the tertile of the highest increase in 25(OH)D level showed a 5.7% BMD gain at lumbar spine, that was twice as great in comparison with participants with a lower 25(OH)D variation. At a multiple regression analysis, BMD change was associated with time since menopause (ß = 2.28, SE 0.44, p < 0.0001), FRAX score for major fracture (ß = −0.65, SE 0.29, p = 0.03), drug holiday duration (ß = −2.17, SE 0.27, p < 0.0001) and change of 25(OH)D levels (ß = 0.15, SE 0.03, p = 0.0007). After ALN discontinuation, improving the vitamin D status boosts the ALN tail effect on BMD.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among premenopausal women. PCOS may have reproductive, metabolic, cardiovascular, and psychological implications. Vitamin D deficit is often encountered in PCOS women and may contribute to the pathophysiology of this disorder. As of the key role of vitamin D in bone and mineral metabolism, and because the vitamin D status appears to be closely linked with the PCOS manifestations including insulin resistance, obesity, ovulatory and menstrual irregularities, oxidative stress and PTH elevation, hypovitaminosis D may directly and indirectly via the different facets of PCOS impair bone health in these women. Although limited data are available on life-long fracture risk in women with PCOS, the importance of preserving bone health in youth and adults to prevent osteoporosis and related fractures is also recognized in PCOS women. Evidence of the association between vitamin D and the clinical hallmarks of PCOS are summarized and discussed. Vitamin D arises as a cornerstone in women with PCOS and contributes to the pathophysiological link between PCOS and bone metabolism.

We report the case of a 67-year-old man admitted to our hospital in an obtunded state. We found that a severe hyponatremia (115 mEq/L) was the cause of patient's status. In turn, hyponatremia was due to hypopituitarism (nonfunctioning macroadenoma). Mild to moderate hyponatremia had been previously detected in this patient, but it was overlooked. Correction of hyponatremia and treatment replacement therapy for central hypothyroidism and hypocortisolism restored a satisfactory clinical condition before discharge. The clinical onset of hypopituitarism is often characterized by mild nonspecific symptoms especially in older people, and it is often overlooked. Hypoglycemia can be another clue to undiagnosed hypopituitarism, and in the reported case, suspicious episodes of hypoglycemia occurred in the months preceding admission. Furthermore, several physicians consider hyponatremia as a normal consequence of aging. Although hyponatremia is a common electrolyte disorder in the elderly, physicians should not forget that it could be the leading manifestation of hypopituitarism. Hypopituitarism may be easily diagnosed, but clinical suspicion is needed. Because of the excess mortality associated with hypopituitarism, hormone assays should be included in the initial diagnostic work-up of hyponatremia. Keywords: Electrolyte balance, Hyponatremia, Hypopituitarism, Adrenal insufficiency, Elderly

There is cumulating evidence for a contribution of Wnt signaling pathways in multiple processes involved in atherosclerosis and vascular aging. Wnt signaling plays a role in endothelial dysfunction, in the proliferation and migration of vascular smooth muscle cells (VSMCs) and intimal thickening. Moreover, it interferes with inflammation processes, monocyte adhesion and migration, as well as with foam cell formation and vascular calcification progression. Sclerostin is a negative regulator of the canonical Wnt signaling pathway and, accordingly, the consequence of increased sclerostin availability can be disruption of the Wnt signalling cascade. Sclerostin is becoming a marker for clinical and subclinical vascular diseases and several lines of evidence illustrate its role in the pathophysiology of the vascular system. Sclerostin levels increase with aging and persist higher in some diseases (e.g., diabetes, chronic kidney disease) that are known to precipitate atherosclerosis and enhance cardiovascular risk. Current knowledge on the association between sclerostin and vascular diseases is summarized in this review.

Vitamin D is tightly linked with renal tubular homeostasis: the mitochondria of proximal convoluted tubule cells are the production site of 1α,25-dihydroxyvitamin D3. Patients with renal impairment or tubular injury often suffer from chronic inflammation. This alteration comes from oxidative stress, acidosis, decreased clearance of inflammatory cytokines and stimulation of inflammatory factors. The challenge is to find the right formula for each patient to correctly modulate the landscape of treatment and preserve the essential functions of the organism without perturbating its homeostasis. The complexity of the counter-regulation mechanisms and the different axis involved in the Vitamin D equilibrium pose a major issue on Vitamin D as a potential effective anti-inflammatory drug. The therapeutic use of this compound should be able to inhibit the development of inflammation without interfering with normal homeostasis. Megalin-Cubilin-Amnionless and the FGF23-Klotho axis represent two Vitamin D-linked mechanisms that could modulate and ameliorate the damage response at the renal tubular level, balancing Vitamin D therapy with an effect potent enough to contrast the inflammatory cascades, but which avoids potential severe side effects.

Quality of life (QoL) represents a dramatic issue in an aging population. Vitamin D has been consistently associated with several diseases. Thus, vitamin D may be considered a hallmark of health status. Our aim was to investigate whether vitamin D could be a determinant of self-perceived quality of life. The 36-Item Short Form Health Survey (SF-36) for quality of life, the Hamilton Anxiety Rating Scale (HAM-A), the Beck Depression Inventory II edition (BDI-II), in addition with multiple clinical risk factors for fractures and FRAX score, BMD at lumbar spine and femoral neck, were evaluated in a group of 177 postmenopausal women referring to an outpatients clinic for the prevention of osteoporosis. Serum levels of vitamin D [25(OH)D], indicative of vitamin D status, were detected by high-performance liquid chromatography. Scores of each dimension of the SF-36 were significantly related with the measurements of anxiety and depression by HAM-A and BDI-II respectively. Moreover role emotional, vitality, general health and bodily pain were significantly associated with vitamin D status. However, at a stepwise multiple regression analysis the physical component summary, obtained from SF-36, was not independently predicted from vitamin D. In conclusion we found an association between vitamin D status and QoL, thus we suggest physicians to consider vitamin D levels as a marker of QoL. Further studies testing the impact of vitamin D administration in improving QoL over time are needed.

Vitamin D status has been previously associated with a wide range of acute and chronic diseases. The nervous system express vitamin D receptors and thus vitamin D may be involved in mental health. Poor data exist about the correlation between vitamin D and anxiety levels.Our aim was to investigate the association of vitamin D status with anxiety severity. A group of 177 postmenopausal women (mean age 65.5±8.22 yr.) referring to an outpatients clinic for the prevention of osteoporosis were evaluated. Severity of perceived anxiety symptoms was measured by the Hamilton Anxiety rating scale (HAMA). Depression levels were also evaluated using the Beck Depression Inventory-second edition scale (BDI-II). 25(OH)D serum levels, indicative of vitamin D status, were detected by high-performance liquid chromatography. 25(OH)D levels were significantly related HAMA-score (r=-0.15, p=0.04); particularly a deep association was observed between 25(OH)D levels and somatic symptoms (r=-0.195, p=0.009). HAMA score was associated with BDI-II score (r=0.487, p=

Anxiety and osteoporosis are common diseases and major public health problems. The association between anxiety levels and bone loss was poorly investigated, thus we aimed to explore whether anxiety severity could be considered as an independent fracture risk. In a setting of postmenopausal women we measured anxiety levels by Hamilton Anxiety Rating Scale (HAMA), depressive symptoms by Beck Depression Inventory and evaluated quality of life by the 36-Item Short Form Health Survey (SF-36) questionnaire. Women with higher anxiety levels showed lower BMD at lumbar spine and femoral neck, and exhibited a poorer quality of life after grouping our population in tertiles of HAMA score. Anxiety levels were predictive of reduced BMD after correcting for other known clinical risk of fractures.

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of osteoporotic fractures, resulting in disabilities and increased mortality. The pathophysiological mechanisms linking diabetes to osteoporosis have not been fully explained, but alterations in bone structure and quality are well described in diabetic subjects, likely due to a combination of different factors. Insulin deficiency and dysfunction, obesity and hyperinsulinemia, altered level of oestrogen, leptin, and adiponectin as well as diabetes-related complications, especially peripheral neuropathy, orthostatic hypotension, or reduced vision due to retinopathy may all be associated with an impairment in bone metabolism and with the increased risk of fractures. Finally, medications commonly used in the treatment of T2DM may have an impact on bone metabolism and on fracture risk, particularly in postmenopausal women. When considering the impact of hypoglycaemic drugs on bone, it is important to balance their potential direct effects on bone quality with the risk of falling-related fractures due to the associated hypoglycaemic risk. In this review, experimental and clinical evidence connecting bone metabolism and fracture risk to T2DM is discussed, with particular emphasis on hypoglycaemic treatments and gender-specific implications.