Frailty modifications and prognostic impact in older patients admitted in acute care.

BACKGROUND: Frailty is a predictor of adverse outcomes in older subjects. AIMS: The aims of this study are to (1) measure the frailty status and its changes occurring during the hospital stay, (2) determine the relationships among frailty and adverse outcomes. METHODS: Frailty was assessed using a 46-item Frailty Index (FI) in 156 patients admitted to an Acute Geriatric Medicine Unit. The FI was calculated within 24 h from the hospital admission (aFI) and at his/her discharge (dFI). Patients were followed up to 12 months after the hospital discharge. RESULTS: A statistically significant difference was reported between the aFI (0.31, IQR 0.19-0.44) and the dFI (0.29, IQR 0.19-0.40; p = 0.04). The aFI was directly associated with the risk of in-hospital death (OR = 5.9; 95% CI 2.0-17.5; p = 0.001), 1 year mortality (OR = 5.5, 95% CI 2.4-12.7, p < 0.001) and re-hospitalization (OR = 6.3, 95% CI 2.2-17.9, p = 0.03). CONCLUSION: Frailty is a strong predictor of negative endpoints in hospitalized older persons. DISCUSSION: Frailty assessment from routinely collected clinical data may provide important insights about the biological status of the individual and promote the personalization of care.

Vitamin D Status and the Relationship with Bone Fragility Fractures in HIV-Infected Patients: A Case Control Study.

HIV-infected patients show high risk of fracture. The aims of our study were to determine the prevalence of vertebral fractures (VFs) and their associations with vitamin D in HIV patients. 100 patients with HIV infection and 100 healthy age- and sex-matched controls were studied. Bone mineral density was measured by quantitative ultrasound at the non-dominant heel. Serum osteocalcin and C-terminal telopeptide of collagen type 1 served as bone turnover markers. Bone ultrasound measurements were significantly lower in patients compared with controls (Stiffness Index (SI): 80.58 ± 19.95% vs. 93.80 ± 7.10%, respectively, p < 0.001). VFs were found in 16 patients and in 2 controls. HIV patients with vertebral fractures showed lower stiffness index (SI) (70.75 ± 10.63 vs. 83.36 ± 16.19, respectively, p = 0.045) and lower vitamin D levels (16.20 ± 5.62 vs. 28.14 ± 11.94, respectively, p < 0.02). The majority of VFs (87.5%) were observed in HIV-infected patients with vitamin D insufficiency, and regression analysis showed that vitamin D insufficiency was significantly associated with vertebral fractures (OR 9.15; 95% CI 0.18-0.52, p < 0.04). VFs and are a frequent occurrence in HIV-infected patients and may be associated with vitamin D insufficiency.

Relationship between blood pressure and frailty in older hypertensive outpatients.

BACKGROUND: The benefits and risks of treating hypertension in old and frail patients are debated. AIM: The aim of the present study is to measure the frailty status in older patients with hypertension and determine the relationships existing between blood pressure (BP) values and frailty. METHODS: Frailty was retrospectively assessed by using the frailty index (FI) in 56 hypertensive old outpatients. Patients with an FI > 0.25 were classified as frail. RESULTS: Forty-five out of 56 (80%) had a FI > 0.25. A statistically significant inverse correlation was found between FI and systolic BP (r = -0.319, p = 0.016), orthostatic systolic BP (r = -0.408, p = 0.002), orthostatic diastolic BP (r = -0.299, p = 0.025), and orthostatic pulse pressure (r = -0.297, p = 0.026). DISCUSSION: Frailer subjects appear as over-treated according to current European guidelines. CONCLUSIONS: FI can play an important role in the clinical setting by supporting the identification of subjects at risk and allowing an improved provision of adapted and personalized care.

Denosumab Inhibition of RANKL and Insulin Resistance in Postmenopausal Women with Osteoporosis.

The tumor necrosis factor-related cytokine receptor activator of nuclear factor kappa B ligand (RANKL) has been proposed as predictor of incident type 2 diabetes mellitus, and experimental blockade of RANKL resulted in a marked improvement of glucose tolerance. Denosumab is a fully human monoclonal antibody that binds to RANKL and prevents osteoclast formation, function and survival, leading to fracture risk reduction. The aim of our study was to investigate glucometabolic parameters, insulin resistance, and lipid profile in non-diabetic women receiving denosumab. Forty-eight women with postmenopausal osteoporosis were enrolled and treated with a subcutaneous dose (60 mg) of denosumab. At baseline and after 4, 12, ad 24 weeks, insulin resistance was computed by homeostasis model assessment of insulin resistance (HOMA-IR) and total cholesterol, triglycerides and HDL cholesterol were also measured. At baseline and after 24 weeks, bone turn-over markers were also evaluated. After denosumab administration, with the exception of a slight reduction of insulin and HOMA-IR values after 4 weeks (p < 0.05), neither fasting plasma glucose nor insulin and insulin resistance were significantly changed. Lipid parameters remained unchanged at each time-points of this study. A reduction of C-telopeptide of type 1 collagen (-63%, p < 0.0001) and osteocalcin (-45%, p < 0.0001), as bone resorption and formation markers, respectively, were observed after 24 weeks. Baseline levels of bone biomarkers were not predictive of HOMA-IR, and changes of osteocalcin were not associated to markers of glucose control. In osteoporotic otherwise healthy postmenopausal women, denosumab was not associated with relevant modification of insulin resistance and lipid profile.

Effects of strontium ranelate on bone mass and bone turnover in women with thalassemia major-related osteoporosis.

Subjects affected by thalassemia major (TM) often have reduced bone mass and increased fracture risk. Strontium ranelate (SrR) is an effective treatment for postmenopausal and male osteoporosis. To date, no data exist on the use of SrR in the treatment of TM-related osteoporosis. Our aim was to evaluate the effects of SrR on bone mineral density (BMD), bone turnover markers and inhibitors of Wnt signaling (sclerostin and DKK-1). Twenty-four TM osteoporotic women were randomized to receive daily SrR 2 g or placebo in addition to calcium carbonate (1,000 mg) and vitamin D (800 IU). BMD at the lumbar spine and femoral neck, bone turnover markers (C-terminal telopeptide of procollagen type I [CTX], bone-specific alkaline phosphatase [BSAP]) and insulin-like growth factor-1 (IGF-1), sclerostin and DKK-1 were assessed at baseline and after 24 months. Back pain was measured by visual analog scale (VAS) every 6 months. After 24 months, TM women treated with SrR had increased their spine BMD values in comparison to baseline (p < 0.05). Moreover, they also exhibited a reduction of CTX and sclerostin levels (but not DKK-1) and exhibited an increase of BSAP and IGF-1 (p < 0.05); however, no significant changes were observed in the placebo group. In the SrR group, a reduction of back pain was observed after 18 months in comparison to baseline (p < 0.05) and after 24 months in comparison to placebo (p < 0.05). Our study reports for the first time the effects of SrR in the treatment of TM-related osteoporosis. SrR treatment improved BMD and normalized bone turnover markers, as well as lowering sclerostin serum levels.

Does Vitamin D3 Have an Impact on Clinical and Biochemical Parameters Related to Third Molar Surgery.

The purpose of this study was to evaluate the clinical effect on the biochemical inflammatory markers of a single oral high dose of cholecalciferol in vitamin D-deficient patients undergoing the surgical removal of lower third molars.A randomized, split-mouth, single-blind study was conducted on 25 vitamin D-deficient patients ranging between 18 and 40 years of age requiring lower third molars extraction and referred at the Oral Surgery Unit of the School of Dentistry of the University of Messina.All patients, with vitamin D3 blood levels ≦30 ng/mL, underwent bilateral surgical removal. The first extraction (control group) being conducted with the administration of a placebo, the second one (test group) being conducted with the preliminary administration of 300,000 IU of cholecalciferol 4 days before the procedure.At each surgery, clinical indexes, such as pain, edema and any functional limitation have been recorded. Clinical and biochemical parameters were registered 4 days before, immediately after, 3 and 7 days after the surgical procedure. The data obtained were processed using paired t-test. The clinical outcome parameters showed a slight to moderate improvement between the control and the vitamin-D treatment group, with statistical significance being obtained regarding the edema at defined time points. Interleukin-1-beta, interleukin-6, and tumor necrosis factor-alpha values were significantly lower (P < 0.01) for the test group after the surgery. The increase of vitamin D serum levels showed an impact on the outcome of the third molar surgery, eliciting a reduced inflammatory response and leading to a more favorable clinical course.

Skin Involvement and Pulmonary Hypertension Are Associated with Vitamin D Insufficiency in Scleroderma.

Vitamin D status has been linked to immune system and autoimmune disorders; in fact, low levels of vitamin D are common in many autoimmune disorders. The aims of our study were to assess the prevalence of vitamin D insufficiency and the possible correlation with clinical parameters in systemic sclerosis (SSc). We recruited 40 patients (38 female and two male) with scleroderma and 40 healthy controls matched for age and gender. Demographic and clinical parameters were recorded and the 25-hydroxivitamin D3 serum levels were measured. Serum 25-hydroxivitamin D3 levels were significantly lower in patients with systemic sclerosis than in the control group. The prevalence of 25-hydroxivitamin D3 insufficiency was 50% in the patients and 22.5% in the control group. A statistically significant association was observed between the insufficiency of 25-hydroxivitamin D3 and skin involvement (p = 0.02) and echocardiography systolic pulmonary artery pressure >35 mmHg (p = 0.02). Our data show that the systemic sclerosis group has significantly lower serum 25-hydroxivitamin D3 concentrations compared to the control group; skin involvement and pulmonary hypertension are associated with vitamin D3 insufficiency.

Calcifediol improves lipid profile in osteopenicatorvastatin-treated postmenopausal women.

BACKGROUND: Low vitamin D serum levels have been associated with unfavourable lipid profile and poorer response to atorvastatin. Aims of this study were to test the effects of 25-hydroxyvitamin D3 (calcifediol) compared to parental vitamin D3 (cholecalciferol) supplementation on modifications of plasma 25(OH)D levels and lipid profile. MATERIALS AND METHODS: Fifty-seven postmenopausal women (aged 59.03 ± 6.73 years) who were at low risk of fracture and with basal plasma 25(OH)D < 30 ng/mL were included if they were on atorvastatin treatment prescribed as appropriate. Recruited women were randomized to receive oral calcifediol or cholecalciferol, both at a dose of 140 µg according to a weekly regimen. RESULTS: At baseline, 25(OH)D was negatively associated with BMI (r = -0.37; P = 0.004), total cholesterol (r = -0.31; P = 0.01) and LDL-C (r = -0.32; P = 0.02). After 24 weeks, 25(OH)D increased significantly in both groups (P < 0.001), although higher levels were obtained with calcifediol as compared with cholecalciferol (P < 0.001). Only in the calcifediol group, a significant reduction of LDL-C (P = 0.01) and an increase of HDL-C (P = 0.02) were obtained, even after adjustment for age, and baseline BMI, 25(OH)D and lipid levels (P < 0.05). The percentage changes in 25(OH)D levels were associated with the variations of LDL-C (r = -0.44; P = 0.01) and HDL-C levels (r = 0.30; P = 0.10). CONCLUSION: Calcifediol administration in osteopenic and dyslipidemic postmenopausal women with low 25(OH)D improves lipid profile when added to an ongoing atorvastatin treatment.

Fracture risk assessment in postmenopausal women referred to an Italian center for osteoporosis: a single day experience in Messina.

Osteoporosis is a major cause of fragility fractures and these are responsible of large social burden; nevertheless, osteoporosis often remains an underdiagnosed disease. FRAX is a new and simple validate fracture risk assessment tool helping physicians to select patients at high risk of future fragility fractures. To promote early diagnosis of osteoporosis, we evaluated fracture risk by FRAX and performed phalangeal quantitative ultrasound (QUS) measurements in a population of postmenopausal women referring to our center during the World Osteoporosis Day on 20th October 2011. Eighty post-menopausal women (age 60.8±8.6) were screened and the risk of major osteoporotic and hip fractures over ten years was calculated by considering multiple clinical risk factors (CRFs). The median risk of major osteoporotic fracture (%) was 4.9 (3.5-8.6) in women younger than 55 years, 7.3 (5.4-11) in women aged between 55 and 65 years and 17.5 (11-27) in women older than 65 years; the median risk of hip fracture (%) was 0.6 (0.3-1.3), 1.5 (0.9-2.5) and 7.2 (3.1-14) respectively. QUS measurements, were lower in the older women and when multiple CRFs coexisted, and were found to correlate with fracture risk, especially with hip fracture risk (p<0.05). Within one month from the screening, 75% (44/59) of the women over 55 years came back and received a diagnosis of osteoporosis/osteopenia by dual x-ray absorptiometry (DXA); a positive association between DXA and QUS measurements was observed (p<0.0001). Adequate treatment of these subjects could reduce fracture rates, improve the quality of life, and reduce the social costs of osteoporosis.

Vitamin D reduces musculoskeletal pain after infusion of zoledronic acid for postmenopausal osteoporosis.

The acute-phase response (APR) is a frequent occurrence after infusion of zoledronic acid and is caused by activation of γδ T cells. Vitamin D receptor is expressed in immune cells, and vitamin D has immunomodulatory properties. The aim of this prospective study was to test the effect of vitamin D (cholecalciferol) on the incidence of APR and intensity of pain in women undergoing infusion of zoledronic acid for postmenopausal osteoporosis. 60 women were enrolled and randomized into two groups. At baseline, 30 women received an oral bolus of cholecalciferol (300,000 IU), while another 30 women received placebo. On day 5 both groups were treated with a single infusion of zoledronic acid (5 mg) and received a daily supplementation of calcium (1,000 mg) and vitamin D (800 IU). Patients were clinically evaluated and inflammatory markers were assayed before zoledronic acid administration and every 24 h for the following 2 days. The onset of APR has been defined by the occurrence of fever or at least one of the typical symptoms, such as musculoskeletal pain after zoledronic acid infusion. Intensity of pain was measured by a one-dimensional scale (0 = no pain, 10 = unbearable pain). APR developed in 66.6% of patients, with no significant difference between groups. The vitamin group experienced less musculoskeletal pain [median 1 (0-4) vs. 2 (1-8), P < 0.05] and exhibited lower inflammatory markers (P < 0.005 vs. placebo). Our data demonstrate that cholecalciferol at a dose of 300,000 IU reduces the intensity of musculoskeletal pain after infusion of zoledronic acid for postmenopausal osteoporosis.

Electrocardiographic changes in centenarians: a study on 42 subjects and comparison with the literature.

BACKGROUND: Aging is associated with extensive and pervasive changes in cardiovascular structure and function, which may result in electrocardiographic alterations. The typical modifications seen in an electrocardiogram (ECG) in elders are: prolonged PR and QT intervals, QRS left-axis deviation and microvolt T wave. Several studies have included elderly people, but not long-living elderly and centenarians in particular who represent an increasing part of the population. OBJECTIVE: The aim of this study was to investigate the electrocardiographic findings in a population of centenarians and to compare the results with the few studies present in the literature. METHODS: We analyzed 42 healthy centenarians (12 males, 30 females; average age 101.43 ± 1.80 years) living in Messina, a municipality of Eastern Sicily, in Italy. They were clinically and functionally evaluated. All ECGs were analyzed by a single observer blind to clinical data. We assessed survival by phone recall. RESULTS: PR interval mean duration was 190 ± 3.3 ms, QRS 90 ± 1.4 ms, QTc interval mean duration was 370 ± 3.5 ms. Entirely normal ECG recordings were found in 7 centenarians (16.6%). The most frequently observed abnormalities included left-axis deviation and left anterior hemiblock in 16 centenarians (38.09%), left ventricular hypertrophy and aspecific ST-T wave abnormalities in 13 subjects (30.95%). We found no statistically significant differences between men and women. The mean age at death was 102.44 ± 2.45, and we did not find significant differences in age at death in long-living elderly in relation to different electrocardiographic findings. Comparing our results with two previous studies in the literature, the first conducted in Switzerland [Cornu: Rev Med Suisse Rom 1979;99:107-113] and the second in Nebraska [Lakkireddy et al.: Am J Cardiol 2003;92:1249-1251], we found a higher frequency of left ventricular hypertrophy that was compatible with the prevalence of hypertension in our centenarians (33.3%). Moreover, we did not find left bundle branch block, and the frequency of premature beats was remarkably less than that observed in the Swiss and US studies. CONCLUSIONS: Considering the increasing rate of centenarians, we believe that the results of the present study on electrocardiographic changes in centenarians may also be useful in clinical practice.

Hypocalcemia: a sometimes overlooked cause of heart failure in the elderly.

Heart failure, a common condition affecting older patients, is associated with increased hospitalization and mortality rates among geriatric patients. We describe the case of an 86-year-old woman with moderate renal failure, who presented pulmonary edema and severe myocardial dysfunction due to hypocalcemia. Renal failure, but also the combination of additional factors, may have contributed to hypocalcemia, including vitamin D deficiency, loop diuretics and glucocorticoid therapy - which alone can give rise to sodium retention and calciuresis, and worsens hypocalcemia. Although in animal experiments hypocalcemia has been shown to lead to cardiac decompensation, heart failure from hypocalcemia is quite rare in clinical practice. Calcium plays a key role in cardiac muscle contraction and metabolism. It is recommended that physicians check serum calcium levels in the elderly, as hypocalcemia is a reversible cause of heart failure.

L-thyroxine malabsorption due to calcium carbonate impairs blood pressure, total cholesterolemia, and fasting glycemia.

PURPOSE: Calcium carbonate was previously shown to interfere with L-thyroxine absorption. To estimate the magnitude of tablet L-thyroxine malabsorption caused by calcium carbonate, with resulting increase in serum thyrotropin (TSH), we performed a cohort study in a referral care center. METHODS: Fifty postmenopausal hypothyroid L-thyroxine-treated women (age 71.7 ± 5.1 years) who added calcium supplementation (600-1000 mg/day) were considered. They were taking L-thyroxine 45-60 min before breakfast (setting 1). After 4.4 ± 2.0 years from initiation of L-thyroxine therapy, they took calcium supplemaentation within 2 h after L-thyroxine taking (setting 2) for 2.3 ± 1.1 years. Hence, we recommended postponing calcium intake 6-8 h after L-thyroxine (setting 3). We evaluated TSH levels, the prevalence of women with elevated TSH (>4.12 mU/L), total cholesterolemia, fasting glycemia, blood pressure, and the prevalence of hypercholesterolemia, hyperglycemia, and hypertension. RESULTS: TSH levels were 3.33 ± 1.93 mU/L versus 1.93 ± 0.51 or 2.16 ± 0.54 comparing setting 2 with setting 1 or 3 (P < 0.001, both). In setting 2, 18% women had elevated TSH versus none in setting 1 or 3 (P < 0.01). Total cholesterolemia, fasting glycemia, systolic, and diastolic blood pressure were also significantly higher in setting 2 compared to settings 1 and 3. For every 1.0 mU/L increase within the TSH range of 0.85-6.9 mU/L, total cholesterolemia, glycemia, systolic, and diastolic blood pressure increased by 12.1, 3.12 mg/dL, 2.31, and 2.0 mmHg, respectively. CONCLUSIONS: Monitoring of hypothyroid patients who ingest medications that decrease L-thyroxine absorption should not be restricted to solely measuring serum TSH.

In thyroxine-replaced hypothyroid postmenopausal women under simultaneous calcium supplementation, switch to oral liquid or softgel capsule L-thyroxine ensures lower serum TSH levels and favorable effects on blood pressure, total cholesterolemia and glycemia.

PURPOSE: In postmenopausal women under L-T4 therapy, which was subsequently accompanied by calcium carbonate (CC) supplementation taken 6-8 h after tablet L-T4, TSH levels were greater than prior to adding CC. Total cholesterolemia [CHOL], fasting glycemia [FG], systolic and diastolic blood pressure [SBP, DBP] were also greater than baseline. Our aim was to explore the effects of either liquid or softgel capsule L-T4, while maintaining CC ingestion 6-8 h, later on TSH levels, CHOL, FG, SBP, and DBP. METHODS: We proposed to 50 hypothyroid postmenopausal women under tablet L-T4 therapy, to switch to either liquid or softgel capsule L-T4 at the same daily dose while maintaining CC ingestion 6-8 h later. Sixteen women accepted [group I; liquid (n = 9), capsule (n = 7)], while 34 continued tablet L-T4 [group II, (n = 34)]. RESULTS: After 3 months, in group I, TSH decreased significantly (1.23 ± 0.49 vs. 1.80 ± 0.37 mU/L, P < 0.01), as did FG (80.7 ± 7.9 vs. 83.4 ± 6.3 mg/dL, P < 0.05); CHOL, SBP, and DBP decreased, though insignificantly. In contrast, in group II, TSH, FG, CHOL, SBP increased insignificantly, and DBP increased borderline significantly (69.7 ± 9 vs. 66.3 ± 6.5, P < 0.10). Compared to baseline (before adding CC), in group I, TSH was significantly lower (P < 0.01) and the other indices similar; in group II, TSH, FG, and SBP were significantly higher (P < 0.05), DBP borderline significantly higher (P < 0.10) and CHOL insignificantly higher. Performance of liquid L-T4 and capsule L-T4 was similar. CONCLUSION: Delaying CC ingestion even by 6-8 h after taking tablet L-T4 is not entirely satisfactory, unlike liquid or softgel L-T4.

Correction: In thyroxine-replaced hypothyroid postmenopausal women under simultaneous calcium supplementation, switch to oral liquid or softgel capsule L-thyroxine ensures lower serum TSH levels and favorable effects on blood pressure, total cholesterolemia and glycemia.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Pathogenesis of Thalassemia Major-associated Osteoporosis: A Review with Insights from Clinical Experience

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/ß-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.

Correction to: Neuropsychological Assessment in Elderly Men with Benign Prostatic Hyperplasia Treated with Dutasteride.

Catalano Antonino, Martino Gabriella, Bellone Federica, Papalia Maria, Lasco Carmen, Basile Giorgio, Sardella Alberto, Nicocia Giacomo, Morabito Nunziata, Lasco Antonino.

Neuropsychological Assessment in Elderly Men with Benign Prostatic Hyperplasia Treated with Dutasteride.

BACKGROUND AND OBJECTIVE: Benign prostatic hyperplasia (BPH) is a common disease found in elderly men and 5α-reductase (5α-R) inhibitors are a commonly used treatment option. 5α-reduced steroids are compounds that play a role in several functions across different organs and systems. In the adult brain, 5α-R accounts for neuroactive steroid production. Whether neuropsychological impairment could be due to dutasteride treatment, a 5α-R inhibitor affecting the production of dihydrotestosterone (DHT), is still unknown. The aim of our study was to investigate neuropsychological features in men receiving dutasteride. METHODS: The Mini Mental State Examination (MMSE), the Clock Drawing Test (CDT), the Frontal Assessment Battery (FAB), the Hamilton Anxiety Rating Scale (HAM-A), the Beck Depression Inventory second edition (BDI-II) and the Short Form-12 (SF-12) questionnaire were administered in order to explore both cognitive impairment and psychological features. RESULTS: In a sample of BPH patients (n = 40; mean age 71.4 ± 7.4 years), men receiving dutasteride showed no significant differences during the neuropsychological assessment in comparison with an age-matched control group, consisting of BPH men not receiving dutasteride (p < 0.05). No significant associations were recorded between treatment duration and any of the administered tests. CONCLUSIONS: This is the first study investigating the neuropsychological features in dutasteride users. Our preliminary data are consistent with the safety of dutasteride under a mental profile.

As Time Goes by: Anxiety Negatively Affects the Perceived Quality of Life in Patients With Type 2 Diabetes of Long Duration.

INTRODUCTION: Age-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. PURPOSE: As 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). METHODS: Forty 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. RESULTS: Participants (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 (ß = -0.55, p = 0.03, SE = 0.25) and HAM-A scores (ß = -0.52, p = 0.04, SE = 0.24). Moreover, both HAM-A (ß = -0.67, p = 0.01, SE = 0.26) and BDI-II (ß = -0.48, p = 0.02, SE = 0.20) scores were independently predictive of MCS. Metabolic control, instead, was not a significant predictor. CONCLUSION: Our 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.

Pulsed electromagnetic fields modulate bone metabolism via RANKL/OPG and Wnt/ß-catenin pathways in women with postmenopausal osteoporosis: A pilot study.

Pulsed electromagnetic fields (PEMFs) have been proven to enhance in vitro and in vivo osteogenesis with unknown mechanism. Aim of our study was to explore whether RANKL/OPG and Wnt/ß-Catenin pathways could be involved in bone response to PEMFs in a setting of postmenopausal osteoporotic women. Forty-three women (mean age 62.8 ±â€¯4.5 yr.) were randomized into two groups. The PEMFs group received PEMFs treatment (50 min treatment session/day, 6 treatment sessions/week, for a total of 25 times), by wearing a specific gilet applied to the trunk and connected to the electromagnetic device (Biosalus, by HSD Srl, Serravalle RSM), while women assigned to control group received sham PEMFs with the same device. BSAP as bone formation and CTX as bone resorption markers, RANKL, OPG, ß-Catenin, DKK-1 and sclerostin were obtained at baseline, after 30 and 60 days. In PEMFs group, BSAP levels significantly increased after 30 and 60 days while CTX concentrations decreased at day 60. RANKL levels significantly decreased after 60 days. OPG was not significantly changed, but the RANKL/OPG ratio significantly decreased at day 30. DKK-1 levels decreased, while ß-catenin concentrations increased after 30 and 60 days (P < 0.05). No significant changes of calcium, phosphorus, creatinine and sclerostin were detected. In the PEMFs group, at day 30, Δsclerostin was associated with ΔRANKL/OPG ratio (r = -0.5, P = 0.03) and ΔDKK-1 was associated with Δß-Catenin (r = -0.47, P = 0.02). In women with postmenopausal osteoporosis, our data provide evidence of a PEMFs modulation of RANKL/OPG and Wnt/ß-Catenin signaling pathways able to explain the metabolic effects of PEMFs on bone.