Interrelations between clinical-psychological features and bone mineral density changes in post-menopausal women undergoing anti-osteoporotic treatment: a two-year follow-up.

Introduction: Psychological 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. Methods: 192 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. Results: At the end of the study, the patients showed a statistically significant increase of both psychic and somatic anxiety (p<0.0001) and exhibited a worsening of depressive symptoms (p<0.0001), whereas HRQoL showed no change. BMD improved and no incident fractures occurred. BMD variation (ΔBMD) at lumbar spine was significantly associated with anxiety levels (r=0.23, p=0.021). Multiple regression analysis showed that both patients' worsening anxiety levels (ß = -0.1283, SE=0.06142, p=0.04) and their treatment adherence (ß=0.09, SE=0.02, p=0.0006) were independently associated with ΔBMD. Discussion: The findings of the current follow-up study suggest that BMD in post-menopausal women undergoing anti-osteoporotic treatment was predicted by treatment adherence and anxiety change over time.

Trabecular bone score and phalangeal quantitative ultrasound are associated with muscle strength and fracture risk in hemodialysis patients.

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 (ß = -15.21, SE = 5.91, p = 0.02) and TBS (ß = -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.

Bone health in Duchenne muscular dystrophy: clinical and biochemical correlates.

PURPOSE: An increased fracture risk is commonly reported in Duchenne muscular dystrophy (DMD). Our aim was to investigate bone mineral density (BMD) and bone turnover, including sclerostin, and their association with markers of cardiac and respiratory performance in a cohort of DMD subjects. METHODS: In this single center, cross sectional observational study, lumbar spine (LS) BMD Z-scores, C-terminal telopeptide of procollagen type I (CTX) and osteocalcin (BGP), as bone resorption and formation markers, respectively, and sclerostin were assessed. Left ventricular ejection fraction (LVEF) and forced vital capacity (FVC) were evaluated. Clinical prevalent fractures were also recorded. RESULTS: Thirty-one patients [median age = 14 (12-21.5) years] were studied. Ambulant subjects had higher LS BMD Z-scores compared with non-ambulant ones and subjects with prevalent clinical fractures [n = 9 (29%)] showed lower LS BMD Z-scores compared with subjects without fractures. LS BMD Z-scores were positively correlated with FVC (r = 0.50; p = 0.01), but not with glucocorticoid use, and FVC was positively associated with BGP (r = 0.55; p = 0.02). In non-ambulant subjects, LS BMD Z-scores were associated with BMI (r = 0.54; p = 0.02) and sclerostin was associated with age (r = 0.44; p = 0.05). Age, BMI, FVC and sclerostin were independently associated with LS BMD Z-score in a stepwise multiple regression analysis. Older age, lower BMI, FVC and sclerostin were associated with lower LS BMD Z-scores. CONCLUSION: In a cohort of DMD patients, our data confirm low LS BMD Z-scores, mainly in non-ambulant subjects and irrespective of the glucocorticoid use, and suggest that FVC and sclerostin are independently associated with LS BMD Z-scores.

Early Changes of VEGF Levels After Zoledronic Acid in Women With Postmenopausal Osteoporosis: A Potential Role of Vitamin D.

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 (ß = 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.

Anxiety Levels Predict Bone Mineral Density in Postmenopausal Women Undergoing Oral Bisphosphonates: A Two-Year Follow-Up.

Clinical psychological factors may predict medical diseases. Anxiety level has been associated with osteoporosis, but its role on bone mineral density (BMD) change is still unknown. This study aimed to investigate the association between anxiety levels and both adherence and treatment response to oral bisphosphonates (BPs) in postmenopausal osteoporosis. BMD and anxiety levels were evaluated trough dual-energy X-ray absorptiometry and the Hamilton Anxiety Rating Scale (HAM-A), respectively. Participants received weekly medication with alendronate or risedronate and were grouped according to the HAM-A scores into tertiles (HAM-A 3 > HAM-A 2 > HAM-A 1). After 24 months, BMD changes were different among the HAM-A tertiles. The median lumbar BMD change was significantly greater in both the HAM-A 2 and HAM-A 3 in comparison with the HAM-A 1. The same trend was observed for femoral BMD change. Adherence to BPs was >75% in 68% of patients in the HAM-A 1, 79% of patients in the HAM-A 2, and 89% of patients in the HAM-A 3 (p = 0.0014). After correcting for age, body mass index, depressive symptoms, and the 10-yr. probability of osteoporotic fractures, anxiety levels independently predicted lumbar BMD change (ß = 0.3417, SE 0.145, p = 0.02). In conclusion, women with higher anxiety levels reported greater BMD improvement, highlighting that anxiety was associated with adherence and response to osteoporosis medical treatment, although further research on this topic is needed.

Vitamin D Boosts Alendronate Tail Effect on Bone Mineral Density in Postmenopausal Women with Osteoporosis.

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.

Rates of hypomagnesemia and hypermagnesemia in medical settings.

Magnesium (Mg) is critically involved in the pathophysiology of multiple human diseases; nevertheless, Mg disorders are often poorly considered in the clinical practice. To update the prevalence and incidence of hypomagnesemia and hypermagnesemia in a real-life scenario, which better represents clinical practice, we analyzed data from 12,696 patients whose Mg serum levels were measured from January 1, 2015, through December 31, 2017 at our University Hospital. Hypomagnesemia and hypermagnesemia were defined by Mg concentrations <1.5 mg/dL (0.6 mmol/L) and >3.8 mg/dL (1.5 mmol/L), in accordance with the reference values for magnesemia of our laboratory (1.5-3.8 mg/dL). The prevalence of hypomagnesemia and hypermagnesemia was 8.43% (n=1071) and 1.78% (n=226), respectively. Hypomagnesemia occurred more frequently in females compared with males [53.3% (n=560) versus 47.7% (n=511), χ2=4.03, p<0.045]; the highest prevalence of hypomagnesemia was found in patients over 65 yr. [59.01% (n=632)], when compared with the other age groups [59.01% (n=632) versus 9.52% (n=102) in patients aged 0-18 yr. and 31.46% (n=337) in patients between 19 and 65 yr., χ2=592.64; p<0.0001)]. Incidence of hypomagnesemia decreased over time in subjects over 65 yr. (r=-0.99; p=0.07). Geriatrics, oncology, and intensive care division showed the highest incidences of hypomagnesemia. Mg disorders and remarkably hypomagnesemia are quite common in the clinical practice, particularly in older hospitalized patients. Thus, they should be routinely checked and corrected.

Sclerostin and Vascular Pathophysiology.

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.

Quality of life and psychological functioning in postmenopausal women undergoing aromatase inhibitor treatment for early breast cancer.

INTRODUCTION: Aromatase 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). PURPOSE: As 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. METHODS: The 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. RESULTS: BCSs (n = 51) showed higher anxious and depressive symptoms, and lower perceived QoL vs. controls (n = 51) (p<0.05 for all). After 6 months of treatment with AIs, BCSs showed significant reduction of anxious and depressive symptoms and a significantly higher perceived QoL for both physical and mental components, vs. controls. CONCLUSIONS: The 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.

Executive functions predict fracture risk in postmenopausal women assessed for osteoporosis.

BACKGROUND: Cognitive impairment and muscle strength have been associated with bone fragility. However, the potential predictive role of executive functions on fracture risk has been poorly investigated. AIM: We intended to explore the association between executive functions, psychological distress and physical performance with fracture risk in postmenopausal women. METHODS: Cognitive tests explicating executive functions (i.e., Trial Making Test-B, Digit Span Backward, Digit Span Forward) and questionnaires assessing psychological distress (i.e., Back Depression Inventory and Hamilton Anxiety Scale) were administered. Physical performance was explored through the Short Physical Performance Battery and handgrip strength. The 10-year probability of major and hip fractures was assessed by Fracture Risk Assessment tool (FRAX); the bone mineral density (BMD) was evaluated by Dual-Energy X-ray Absorptiometry. RESULTS: 60 women (mean age 66 ± 7.99 yr.) were recruited. The FRAX score for major fractures was significantly associated with Trial Making Test B score (r = - 0.25) and with Digit Span Backward (r = - 0.34); the FRAX score for hip fracture was associated with handgrip strength (r = - 0.39, p = 0.002). BMD was significantly associated with Digit Span Backward (r = - 0.32) and with depression (r = - 0.33). After several adjustments, the multiple regression analysis showed that BMI (ß = 0.09, SE 0.03, p = 0.013), Beck Depression Inventory score (ß = - 0.09, SE 0.06, p = 0.04) and Digit Span Backward score (ß = 0.55, SE 0.17, p = 0.002) were independently predictive of lumbar BMD. CONCLUSIONS: Verbal working memory, as assessed by Digit Span Test, and psychological features were associated with BMD and could contribute to fracture risk prediction in postmenopausal women.

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.

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.

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.

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.

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.

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.

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.

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.

Anxiety levels predict fracture risk in postmenopausal women assessed for osteoporosis.

OBJECTIVE: There has been increasing interest in the association of psychiatric disorders with fracture risk. This study aimed at investigating the role of severity of anxiety in bone health. METHODS: Multiple clinical risk factors for fractures, the Fracture Risk Assessment Tool score, the bone mineral density (BMD) at the lumbar spine and femoral neck, Hamilton Anxiety Rating Scale (HAMA) scores, Beck Depression Inventory scores, and the 36-Item Short Form Health Survey (SF-36) scores for evaluation of the quality of life were determined, and x-ray vertebral morphometry was carried out in postmenopausal women referred for osteoporosis. RESULTS: Of the 192 women recruited (mean age 67.5 ±â€Š9.5 years), participants allocated to the tertile of the lowest HAMA scores (HAMA-1) showed a lower probability of fracture than did participants with the highest scores (HAMA-3) (20.44 ±â€Š9.3 vs 24.94 ±â€Š13%, respectively; P = 0.01), and the same trend was observed when comparing the HAMA-2 and HAMA-3 tertiles. Women in the HAMA-3 group exhibited lower lumbar T-score vales in the lumbar spine than did women in the HAMA-1 group (-2.84 ±â€Š1.4 vs -2.06 ±â€Š1.2 SD, respectively; P < 0.001) and a lower T-score value in the femoral neck (-2.21 ±â€Š0.9 vs -1.93 ±â€Š0.6 SD, respectively; P < 0.05). Lower T-score values were observed in HAMA-3 than in HAMA-2. A higher prevalence rate of vertebral fractures was observed in HAMA-3 than in HAMA-1, but the difference was not significant. Anxiety levels were significantly related to age, menopausal age, years since menopause, and depressive symptoms, and a multiple regression analysis was predictive of reduced BMD in the lumbar spine (ß = -0.00672, SE = 0.001, P = 0.0002). CONCLUSION: In postmenopausal women, anxiety levels were associated with BMD in the lumbar spine and femoral neck.