Is the relationship between erythropoiesis and renal function one of the secrets of extreme longevity?

BACKGROUND AND AIMS: Renal function and erythropoiesis could be impaired with advancing age. Neutrophil gelatinase-associated lipocalin (NGAL) as well as erythropoietin (EPO) levels are two useful biomarkers of the renal status. In advanced age, the relationships between NGAL, EPO and hemoglobin (Hb) levels remains unknown. The aim of the present study is to evaluate the relationship between renal function and erythropoiesis in a small cohort of centenarians. METHODS AND RESULTS: We observed thirty-one healthy centenarians with normal hemoglobin levels, a mild reduction in eGFR and no need of erythropoiesis support. We found a significant inverse association between NGAL and GFR, hemoglobin levels and EPO, confirming the key role of the renal function on erythropoiesis also in extreme longevity. A gender difference emerged, showing female participants with lower eGFR and Hb values more than males. CONCLUSIONS: Our findings suggested a new link between renal function, erythropoiesis and longevity in centenarians and these could have relevant implications in clinical practice. These findings could explain why very old subjects presenting a slight GFR reduction seemed not to be exposed to a significant risk of mortality.

Haemophilia and Fragility Fractures: From Pathogenesis to Multidisciplinary Approach.

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.

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.

Changes in Cognitive and Functional Status and in Quality of Life of Older Outpatients during the COVID-19 Pandemic.

BACKGROUND: Older adults denoted one of the populations that mostly suffered from the consequences of the COVID-19 pandemic. The cost of confinement was paid in terms of social isolation, distance from relatives and friends, lack of social support, and limited access to the healthcare system, which had a negative impact on health of older adults with comorbidities and frailty. OBJECTIVES: The purpose of the present study was to report the consequences of the COVID-19 pandemic on cognitive performances, functional status, and health-related quality of life among frail outpatients, compared to pre-pandemic status. METHOD: The current sample was part of a larger sample of frail and pre-frail outpatients, who were first evaluated at the clinic between April and May 2019 and who underwent a first follow-up evaluation between April and May 2020. Those outpatients who have undergone the first follow-up evaluation were contacted between April and May 2021 and were asked to voluntarily participate in a second telephone-based evaluation. Cognitive performances (through Mini Mental State Examination - MMSE), functional independency in basic and instrumental daily activities, physical and mental components of health-related quality of life (SF-12 PCS and SF-12 MCS, respectively) were evaluated and compared to previous evaluations. RESULTS: Seventy one outpatients (mean age of 80.69 years) completed the present follow-up evaluation. Patients reported significantly lower cognitive performances (mean MMSE 19.37; p < 0.001), lower physical quality of life (mean score 31.69; p < 0.001), and lower mental quality of life (mean score 38.79; p < 0.001) compared to both pre-pandemic baseline and the first follow-up. Moreover, patients showed a significantly reduced independency in basic daily activities (mean score 3.8; p = 0.004), and a significantly reduced independency in managing telephone (p = 0.012) and medications (p = 0.035), compared to baseline. CONCLUSIONS: The COVID-19 pandemic has been a prolonged stressor over time, which has markedly affected health-related quality of life of outpatients, and it can be considered a stressor that might have contributed to the patients' greater cognitive and functional vulnerability.

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.

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.

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.

Multiple fractures and impaired bone metabolism in Wolfram syndrome: a case report.

Wolfram Syndrome (WS) is a rare and lethal disease characterized by optic atrophy, diabetes mellitus, diabetes insipidus, and hearing loss. To date, osteoporotic related fractures have not been reported in affected patients. Here, we describe the case of a man affected by WS complicated by several bone fragility fractures. A 50-year-old Caucasian man was hospitalized because of tibia and fibula fractures. His clinical features included diabetes mellitus, diabetes insipidus, optic atrophy and deafness that were consistent with an unrecognized WS diagnosis, which was confirmed by the identification of a specific mutation in gene WFS1 encoding wolframin. Bone mineral density by phalangeal quantitative ultrasound demonstrated severe osteoporosis, with high serum levels of surrogate markers of bone turn-over. Previously unidentified rib fractures were also detected. To the best of our knowledge, this is the first report of osteoporotic related fractures in a patient affected by WS. Although no effective treatments are currently available to delay the progression of the disease, this case report suggests to evaluate fracture risk in the diagnostic work-up of WS.

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.

Nutraceuticals as Alternative Approach against Cadmium-Induced Kidney Damage: A Narrative Review.

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.

Alexithymia and asthma: a systematic review.

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.

Psychological impairment in inflammatory bowel diseases: the key role of coping and defense mechanisms.

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.

Trabecular bone score, bone marrow fat and vertebral fractures in cushing syndrome.

OBJECTIVE: Prediction of fragility fractures in Cushing syndrome (CS) is a challenge since dual energy X-ray absorptiometry (DXA) measurement of bone mineral density (BMD) does not capture all the alterations in bone microstructure induced by glucocorticoid excess. In this study we investigated the relationship between trabecular bone score (TBS), bone marrow fat (BMF) and vertebral fractures (VFs) in endogenous CS. DESIGN: Cross-sectional. METHODS: Thirty subjects (7 M and 23 F, mean age 44.8 ± 13.4 yrs, range: 25-71) with active hypercortisolism were evaluated for VFs by quantitative morphometry, BMD and TBS by lumbar spine DXA and BMF by single-voxel magnetic resonance spectroscopy of vertebral body of L3. RESULTS: Subjects with VFs (17 cases; 56.7%) had higher BMF (P = 0.014) and lower BMD T-score (P = 0.012) and TBS (P = 0.004) as compared to those without VFs. Prevalence of VFs resulted to be significantly higher in individuals with impaired TBS as compared to those with normal TBS (77.8% vs. 25.0%; P = 0.008). Among patients with VFs, only 6 (35.3%) had either osteoporosis or "low BMD for age". In logistic regression analysis, impaired TBS maintained the significant association with VFs [odds ratio (OR) 6.60, 95% C.I. 1.07-40.61; P = 0.042] independently of BMF (OR 1.03, 95% C.I. 0.99-1.08; P = 0.152). CONCLUSIONS: TBS might be more accurate than BMF in identifying subjects with active CS and skeletal fragility at risk of VFs. SIGNIFICANCE STATEMENT: Excess in glucocorticoids is associated with alterations in bone remodeling and metabolism, leading to fragility fractures regardless of bone mineral density, making more challenging for the clinician the identification of high-risk population and the definition of preventing strategies. In this context, instrumental parameters suggestive of bone quality alterations and predictive of increased fracture risk are needed. In this study, we found CS patients to have bone quality alterations as indicated by the decreased trabecular bone score and increased bone marrow fat, as measured by DEXA and MRI respectively. Both parameters were associated with high risk of VFs, and were inversely correlated, although TBS seems to be more accurate than BMF in fractures prediction in this clinical setting.