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Trabecular bone score and phalangeal quantitative ultrasound are associated with muscle strength and fracture risk in hemodialysis patients.
Catalano, A, Gaudio, A, Bellone, F, La Fauci, MM, Xourafa, A, Gembillo, G, Basile, G, Natale, G, Squadrito, G, Corica, F, et al
Frontiers in endocrinology. 2022;:940040
Abstract
There is growing interest in the relationship between chronic kidney disease (CKD) and fragility fracture risk. Bone mineral density (BMD) is a major determinant of bone strength, although its role as a predictor of fracture in advanced CKD and hemodialysis is still under debate. We aimed to further investigate surrogates of bone quality and their associations with muscle strength and fracture risk in hemodialysis. Multiple clinical risk factors for fracture and an estimated 10-year probability of fracture, BMD at lumbar spine and femur, trabecular bone score (TBS), X-ray vertebral morphometry, phalangeal bone quantitative ultrasonography (QUS), tibial pulse-echo ultrasonography (PEUS), and handgrip strength were evaluated in a setting of hemodialysis patients in treatment with acetate-free biofiltration (AFB) or bicarbonate hemodialysis. The bone ultrasound measurements, both at phalangeal and tibial sites, were significantly associated with lumbar and femoral DXA values. Handgrip strength was significantly associated with the 10-year probability of fracture (r = -0.57, p < 0.001 for major fractures and r = -0.53, p < 0.001 for hip fracture, respectively), with femur neck, total femur, and L1-L4 BMD values (r = 0.47, p = 0.04; r = 0.48, p = 0.02; r = 0.58, p = 0.007, respectively), with TBS at the lumbar spine (r = 0.71, p < 0.001) and with the phalangeal QUS measure of AD-SoS (r = 0.369, p = 0.023). In the hemodialysis group, 10 participants (24.3%) reported at least one morphometric vertebral fracture (Vfx); conversely, only six participants (15%) showed Vfx in the control group. In the hemodialysis group, participants with Vfx compared with participants without Vfx reported significantly different TBS, bone transmission time (BTT), cortical thickness, and handgrip strength (p < 0.05). At multiple regression analysis, by identifying as dependent variable the 10-year fracture risk for major fracture, after correcting for age, BMI, time since dialysis, AD-SoS, cortical bone thickness, and handgrip strength, only BTT (β = -15.21, SE = 5.91, p = 0.02) and TBS (β = -54.69, SE = 21.88, p = 0.02) turned out as independently associated with fracture risk. In conclusion, hemodialysis patients showed a higher fracture risk and lower surrogate indices of bone strength as TBS and QUS parameters. In this cohort of patients, handgrip strength measurements appeared to be a useful instrument to identify high-fracture-risk subjects.
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The association between hypoparathyroidism and cognitive impairment: a systematic review.
Sardella, A, Bellone, F, Morabito, N, Minisola, S, Basile, G, Corica, F, Catalano, A
Journal of endocrinological investigation. 2021;(5):905-919
Abstract
CONTEXT AND PURPOSE Hypocalcemia and low parathyroid hormone levels have been commonly suggested as factors able to induce central nervous system disturbances. However, evidences on the occurrence of cognitive impairment are limited or underestimated. The aim of this review is, therefore, to systematically summarize the available evidence concerning the occurrence of cognitive impairment among subjects suffering from idiopathic or secondary hypoparathyroidism. METHODS A systematic selection of the available literature was performed by searching the online databases PubMed, Scopus and Web of Knowledge. RESULTS The present systematic review included sixteen case report articles and one cross-sectional controlled study. Case reports were the most representative literature sources and involved ten women and seven men. The presence of cognitive impairment was mostly discussed in association with idiopathic hypoparathyroidism (HPT); five articles described the occurrence of cognitive impairment following postsurgical HPT. The case-controlled study reported a significant presence of peculiar cognitive deficits (e.g. reduced inhibitory control, impairment in visuo-spatial functioning among, and psychomotor retardation) among HPT subjects compared to healthy controls, with serum total calcium and its product with phosphorus as independent predictors of neuropsychological dysfunctions. CONCLUSION Even though mostly based on single case reports, the presence of neuropsychological dysfunctions in the context of HPT appears to be a consistent core finding.
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Vitamin D Boosts Alendronate Tail Effect on Bone Mineral Density in Postmenopausal Women with Osteoporosis.
Catalano, A, Bellone, F, Santoro, D, Schwarz, P, Gaudio, A, Basile, G, Sottile, MC, Stoian, SA, Corica, F, Morabito, N
Nutrients. 2021;13(6)
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Post-menopausal women are at an increased risk for bone associated disorders such as osteoporosis. Treatments with drugs known as bisphosphonates aim to increase bone density, bone strength, and reduce bone fractures. However long-term treatment may be associated with poor outcomes and short treatment breaks where use is discontinued, may be of benefit. Vitamin D, which has shown to be of benefit during treatment with bisphosphonates, may be of increased importance during these treatment breaks. This retrospective study of postmenopausal women aimed to determine if vitamin D status influenced bone density after osteoporosis treatment had ceased in 1686 patients. The results showed that in those who discontinued osteoporosis treatment, individuals with the highest levels of vitamin D had a greater increase in bone mineral density. Bone density was also associated with a change in vitamin D level. It was concluded that in those who have discontinued osteoporosis treatment improving vitamin D status may be of benefit to bone density. This study could be used by healthcare professionals to understand how vitamin D supplementation may be of benefit in osteoporotic, post-menopausal women who have stopped treatment due to worries of long-term side effects.
Abstract
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.
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Early Changes of VEGF Levels After Zoledronic Acid in Women With Postmenopausal Osteoporosis: A Potential Role of Vitamin D.
Bellone, F, Catalano, A, Sottile, AR, Gaudio, A, Loddo, S, Corica, F, Morabito, N
Frontiers in medicine. 2021;:748438
Abstract
Zoledronic acid (Zol) is a widely used intravenous aminobisphosphonate to treat both benign and malignant skeletal diseases, and bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious side effect whose pathophysiology remains poorly understood. Vascular Endothelial Growth Factor (VEGF) has been recognized to mediate BRONJ in cancer patients undergoing Zol treatment, however data on VEGF are lacking in patients with osteoporosis. Increasing evidences demonstrate that vitamin D influences VEGF levels. The aim of this study was to investigate the influence of Zol on VEGF levels and the possible role for vitamin D on the Zol mediated changes of VEGF concentration in women with postmenopausal osteoporosis. Twenty-eight postmenopausal women with osteoporosis were enrolled and randomized into two groups to receive Zol (5 mg) or placebo. At baseline, at day-3 and day-30 VEGF serum levels were measured; bone turnover markers, 25-hydroxyvitamin D [25(OH)D] and serum calcium were evaluated at baseline. In Zol-treated women, VEGF increased significantly on day-3, and then decreased on day-30. In the Zol-treated women, the percent change of VEGF levels between baseline and day-30 (-18% at day-30 vs. baseline, p = 0.01) was significantly associated with serum 25(OH)D values (r = 0.29, p = 0.028). At a stepwise multiple regression analysis, after correcting for age, BMI, time since menopause, femoral neck BMD, osteocalcin, C-terminal telopeptide of type 1 collagen, and baseline VEGF levels, 25(OH)D levels were independently associated with VEGF change (β = 1.7, SE = 0.71, p = 0.03). For the first time, we detected early modifications of circulating VEGF in postmenopausal women receiving Zol for osteoporosis, identifying a vitamin D-dependent modulation of these changes.
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Quality of life and psychological functioning in postmenopausal women undergoing aromatase inhibitor treatment for early breast cancer.
Martino, G, Catalano, A, Agostino, RM, Bellone, F, Morabito, N, Lasco, CG, Vicario, CM, Schwarz, P, Feldt-Rasmussen, U
PloS one. 2020;(3):e0230681
Abstract
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.
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L-thyroxine malabsorption due to calcium carbonate impairs blood pressure, total cholesterolemia, and fasting glycemia.
Morini, E, Catalano, A, Lasco, A, Morabito, N, Benvenga, S
Endocrine. 2019;(2):284-292
Abstract
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.
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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.
Morini, E, Catalano, A, Lasco, A, Morabito, N, Benvenga, S
Endocrine. 2019;(3):569-579
Abstract
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.
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Pathogenesis of Thalassemia Major-associated Osteoporosis: A Review with Insights from Clinical Experience.
Gaudio, A, Morabito, N, Catalano, A, Rapisarda, R, Xourafa, A, Lasco, A
Journal of clinical research in pediatric endocrinology. 2019;(2):110-117
Abstract
Due to increasing life expectancy in thalassemia major (TM), osteoporosis is emerging as a significant problem. Its aetiology is multifactorial, culminating in increased bone resorption and impaired remodelling. Hypogonadism and marrow expansion seem to play an important role, but iron overload, deferoxamine toxicity, a defective growth hormone-insulin-like growth factor-1 axis and multiple endocrinopathies may represent additional causes of bone damage. Many of these patients, though under appropriate treatment programs, do not achieve normal peak bone mass. The receptor activator of nuclear factor kappa-ß (RANK)/RANK ligand/osteoprotegerin and the Wnt/β-catenin systems work as major mediators of imbalanced bone turnover and bone loss. Additional genetic factors, such as collagen type 1 alpha 1 and vitamin D receptor gene polymorphisms, may exert some influence on the enhanced fracture risk observed in TM. To date, in spite of adequate hormone replacement, chelating therapy and acceptable haemoglobin levels, subjects with TM display impaired bone density and imbalanced bone turnover, thus the puzzle of the pathogenesis of TM-induced osteoporosis remains far from being solved.
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Incidence of hypocalcemia and hypercalcemia in hospitalized patients: Is it changing?
Catalano, A, Chilà, D, Bellone, F, Nicocia, G, Martino, G, Loddo, I, Morabito, N, Benvenga, S, Loddo, S
Journal of clinical & translational endocrinology. 2018;:9-13
Abstract
Disorders of calcium metabolism are frequently encountered in routine clinical practice. However limited data are available on the epidemiology of hypocalcemia and hypercalcemia in hospitalized patients. Our aim was to evaluate the frequency of hypocalcemia and hypercalcemia in hospitalized patients. This is a retrospective study based on the laboratory results of all hospitalized subjects (n = 12,334) whose calcemia was determined between January 1st, 2011 and December 31st, 2014. Measurements of serum calcium were carried out by a single centralized laboratory. Hypocalcemia was defined as serum calcium levels <8.2 mg/dl and hypercalcemia as serum calcium levels >10.4 mg/dl. Albumin correction was applied to adjust serum calcium values. Overall, hypocalcemia accounted for 27.72% (n = 3420) and hypercalcemia for 4.74% (n = 585) of the 12,334 inpatients. The highest prevalence of hypocalcemia was found in patients over 65 yr. (n = 2097, 61.31%) vs. younger subjects, while the highest prevalence of hypercalcemia was observed in patients aged 0-18 yr. (n = 380, 64.95%). Hypocalcemia was more often encountered in males (n = 1952, 57.07%) while no gender differences were found regarding hypercalcemia. Incidence of hypocalcemia changed over time varying from 35.42% (n = 1061) in 2011 to 21.93% (n = 672) in 2014 (r = -0.98; p = 0.01). Differently, incidence of hypercalcemia did not significantly increase significantly from 3.47% (n = 104) in 2011 to 6.92% (n = 211) in 2014 (r = 0.94; p = 0.052). Despite increased awareness about electrolytes disturbance, physicians should consider calcium levels because of life-threatening consequences associated to hypo- and hypercalcemia. Patient's gender and age could be associated to a different risk of calcium disturbance in hospitalized patients.
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Pulsed electromagnetic fields modulate bone metabolism via RANKL/OPG and Wnt/β-catenin pathways in women with postmenopausal osteoporosis: A pilot study.
Catalano, A, Loddo, S, Bellone, F, Pecora, C, Lasco, A, Morabito, N
Bone. 2018;:42-46
Abstract
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/β-Catenin pathways could be involved in bone response to PEMFs in a setting of postmenopausal osteoporotic women. Forty-three women (mean age 62.8 ± 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, β-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 β-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 Δβ-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/β-Catenin signaling pathways able to explain the metabolic effects of PEMFs on bone.