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1.
Ann Rheum Dis ; 83(4): 529-536, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38123339

ABSTRACT

INTRODUCTION: Paget's disease of bone (PDB) frequently presents at an advanced stage with irreversible skeletal damage. Clinical outcomes might be improved by earlier diagnosis and prophylactic treatment. METHODS: We randomised 222 individuals at increased risk of PDB because of pathogenic SQSTM1 variants to receive 5 mg zoledronic acid (ZA) or placebo. The primary outcome was new bone lesions assessed by radionuclide bone scan. Secondary outcomes included change in existing lesions, biochemical markers of bone turnover and skeletal events related to PDB. RESULTS: The median duration of follow-up was 84 months (range 0-127) and 180 participants (81%) completed the study. At baseline, 9 (8.1%) of the ZA group had PDB lesions vs 12 (10.8%) of the placebo group. Two of the placebo group developed new lesions versus none in the ZA group (OR 0.41, 95% CI 0.00 to 3.43, p=0.25). Eight of the placebo group had a poor outcome (lesions which were new, unchanged or progressing) compared with none of the ZA group (OR 0.08, 95% CI 0.00 to 0.42, p=0.003). At the study end, 1 participant in the ZA group had lesions compared with 11 in the placebo group. Biochemical markers of bone turnover were significantly reduced in the ZA group. One participant allocated to placebo required rescue therapy with ZA because of symptomatic disease. The number and severity of adverse events did not differ between groups. CONCLUSIONS: Genetic testing for pathogenic SQSTM1 variants coupled with intervention with ZA is well tolerated and has favourable effects on the progression of early PDB. TRIAL REGISTRATION NUMBER: ISRCTN11616770.


Subject(s)
Diphosphonates , Osteitis Deformans , Humans , Diphosphonates/adverse effects , Osteitis Deformans/complications , Osteitis Deformans/drug therapy , Osteitis Deformans/genetics , Sequestosome-1 Protein/genetics , Zoledronic Acid/therapeutic use , Genetic Testing , Biomarkers
2.
J Bone Miner Res ; 35(7): 1246-1252, 2020 07.
Article in English | MEDLINE | ID: mdl-32176830

ABSTRACT

Mutations in SQSTM1 are strongly associated with Paget's disease of bone (PDB), but little is known about the clinical characteristics of those with early disease. Radionuclide bone scans, biochemical markers of bone turnover, and clinical characteristics were analyzed in SQSTM1 mutation carriers who took part in the Zoledronic acid in the Prevention of Paget's disease (ZiPP) study. We studied 222 individuals, of whom 54.9% were female, with mean ± SE age of 50.1 ± 0.6 years. Twelve SQSTM1 mutations were observed, including p.Pro392Leu, which was present in 141 of 222 (63.5%) subjects. Bone scan examination revealed evidence of PDB in 20 subjects (9.0%), ten of whom (50%) had a single affected site. Participants with lesions were older than those without lesions but the difference was not significant (53.6 ± 9.1 versus 49.8 ± 8.9; p = .07). The mean age of participants with lesions was not significantly different from the age at which their parents were diagnosed with PDB (55 years versus 59 years, p = .17). All individuals with lesions were asymptomatic. Serum concentrations of total alkaline phosphatase (ALP) normalized to the upper limit of normal in each center were higher in those with lesions (0.75 ± 0.69 versus 0.42 ± 0.29 arbitary units; p < .0001). Similar findings were observed for other biochemical markers of bone turnover, but the sensitivity of ALP and other markers in detecting lesions was poor. Asymptomatic PDB is present in about 9% of SQSTM1 mutation carriers by the fifth decade. Further follow-up of this cohort will provide important information on the natural history of early PDB and its response to treatment. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.


Subject(s)
Adaptor Proteins, Signal Transducing , Osteitis Deformans , Sequestosome-1 Protein , Adaptor Proteins, Signal Transducing/genetics , Female , Humans , Male , Middle Aged , Mutation , Osteitis Deformans/epidemiology , Osteitis Deformans/genetics , Sequestosome-1 Protein/genetics , Zoledronic Acid
3.
Calcif Tissue Int ; 106(6): 599-607, 2020 06.
Article in English | MEDLINE | ID: mdl-32076748

ABSTRACT

PURPOSE: Hyponatremia and hypokalemia are common among elderly and have been associated with osteoporosis, we evaluate the role of these electrolytes as risk for fragility fractures. METHODS: This study is divided in two parts: one retrospective and one prospective. We retrospectively collected data on urgently admitted patients for femoral fragility fractures (Fx) or for acute myocardial infarction (AMI), and patients admitted for elective hip/knee replacement surgery for osteoarthrosis (OA). Age, sex, serum sodium, potassium, creatinine, and comorbidities were recorded. We enrolled prospectively in-patients from our unit: age, sex, comorbidities, drugs, and fragility fractures were recorded. Blood electrolytes were measured. Cognitive function, nutrition, muscular strength, and balance were evaluated by standard tests. The mortality rate was recorded with a follow-up after hospital discharge. RESULTS: The retrospective study included 2166 subjects: 702 Fx and 1464 controls (907 AMI, 557 OA): the prevalence of hyponatremia was similar in Fx and AMI, whereas it was higher in Fx with respect to OA (p < 0.001) as well as hypokalemia (p < 0.001). Sodium decrease was associated with higher fracture risk. Among the 284 subjects included in the prospective study, 50 patients were hyponatremic, more likely malnourished, and presented a higher prevalence of fragility fractures (p = 0.008). They had a higher mortality after hospital discharge (HR = 1.80, p = 0.005), however, this association disappears after correction for confounding variables. CONCLUSIONS: We suggest that hyponatremia and hypokalemia have to be considered as a marker of poor health more than an independent fracture risk.


Subject(s)
Hypokalemia , Hyponatremia , Osteoporotic Fractures/complications , Aged , Creatinine/blood , Femur , Humans , Hypokalemia/complications , Hyponatremia/complications , Potassium/blood , Prospective Studies , Retrospective Studies , Risk Factors , Sodium/blood
4.
Neurocase ; 25(6): 259-262, 2019 12.
Article in English | MEDLINE | ID: mdl-31522586

ABSTRACT

Purpose: o report and describe cognitive impairments during lenalidomide treatment in three patients. Despite the relevant clinical impact of chemotherapy-related cognitive deficit (known as "chemobrain effect"), very few data are available in the literature. Methods: We present three subjects who developed cognitive impairment during treatment with lenalidomide. Their neuropsychological assessment was evaluated in order to better define the cognitive areas involved. For each patient medical history, drug therapy, physical examination and other instrumental tests (brain CT scan and/or MRI scan, FDG-PET and electroencephalography) were collected. Results: In all patients, we observed an homogeneous neuropsychological pattern characterized by long-term verbal and visuospatial memory deficits, and decline in attentional and executive functions. Conclusions: Lenalidomide treatments can determine severe cognitive impairments especially in elderly patients. Our data suggest the need for a careful evaluation of cognitive decline risk before and after drug administration. However, larger studies are required to confirm our findings.


Subject(s)
Antineoplastic Agents/adverse effects , Cognitive Dysfunction/chemically induced , Lenalidomide/adverse effects , Multiple Myeloma/drug therapy , Multiple Myeloma/psychology , Aged , Female , Humans , Male , Multiple Myeloma/complications , Neuropsychological Tests
5.
Intern Emerg Med ; 14(1): 85-102, 2019 Jan.
Article in English | MEDLINE | ID: mdl-29948835

ABSTRACT

The purpose of this document, a result of the harmonisation and revision of Guidelines published separately by the SIMFER, SIOMMMS/SIR, and SIOT associations, is to provide practical indications based on specific levels of evidence and various grades of recommendations, drawn from available literature, for the management of osteoporosis and for the diagnosis, prevention, and treatment of fragility fractures. These indications were discussed and formally approved by the delegates of the Italian Scientific Associations involved in the project (SIE, SIGG, SIMFER, SIMG, SIMI, SIOMMMS, SIR, and SIOT).


Subject(s)
Osteoporosis/complications , Osteoporosis/therapy , Osteoporotic Fractures/therapy , Bone Density/physiology , Humans , Italy
6.
Blood Purif ; 46(4): 332-336, 2018.
Article in English | MEDLINE | ID: mdl-30176676

ABSTRACT

BACKGROUND: Acute kidney injury (AKI) incidence is reported to be 10 times higher in aged people. Related to their higher prevalence of chronic kidney disease (CKD), older patients are at high risk of toxic effects driven by drugs. METHODS: The demographics, hospitalizations, visits to the Emergency Department, pharmacological therapy, and lab tests were analyzed in 71,588 individuals. RESULTS: Data showed a higher prevalence of AKI as well as CKD in the elderly as compared to the younger group, with an associated very high mortality. A broad number of drugs was prescribed, ranging from 1 to 35, the majority being between 5 and 9 drugs. CONCLUSION: Elderly patients who developed AKI had a higher number of hospitalizations (underlying frailty), were more likely to progress to more severe stages of CKD and to be affected by other non-renal pathologies (associated comorbidities) and to be given heavier pharmacological prescriptions (polypharmacy).


Subject(s)
Acute Kidney Injury , Hospitalization , Polypharmacy , Renal Insufficiency, Chronic , Acute Kidney Injury/chemically induced , Acute Kidney Injury/epidemiology , Acute Kidney Injury/therapy , Age Factors , Aged , Aged, 80 and over , Female , Humans , Male , Prevalence , Renal Insufficiency, Chronic/chemically induced , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/therapy
7.
BMC Endocr Disord ; 18(1): 55, 2018 Aug 08.
Article in English | MEDLINE | ID: mdl-30089481

ABSTRACT

BACKGROUND: Here we study the effect of type 2 diabetes (T2DM) on bone cell precursors, turnover and cytokines involved in the control of bone cell formation and activity. METHODS: We enrolled in the study 21 T2DM women and 21 non diabetic controls matched for age and body mass index (BMI). In each subject we measured bone cell precursors, Receptor Activator of Nuclear Factor κB (RANKL), Osteoprotegerin (OPG), Sclerostin (SCL) and Dickoppf-1 (DKK-1) as cytokines involved in the control of osteoblast and osteoclast formation and activity, bone density (BMD) and quality trough trabecular bone score (TBS) and bone turnover. T2DM patients and controls were compared for the analyzed variables by one way ANOVA for Gaussian ones and by Mann-Whitney or Kruskal-Wallis test for non-Gaussian variables. RESULTS: RANKL was decreased and DKK-1 increased in T2DM. Accordingly, patients with T2DM have lower bone turnover compared to controls. BMD and TBS were not significantly different from healthy controls. Bone precursor cells were more immature in T2DM. However the number of osteoclast precursors was increased and that of osteoblasts decreased. CONCLUSIONS: Patients with T2DM have more immature bone cells precursors, with increased number of osteoclasts and decreased osteoblasts, confirming low bone turnover and reduced cytokines such as RANKL and DKK-1. BMD and TBS are not significantly altered in T2DM although, in contrast with other studies, this may be due to the match of patients and controls for BMI rather than age.


Subject(s)
Bone Remodeling/physiology , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/diagnosis , Osteoblasts/metabolism , Osteoclasts/metabolism , Aged , Biomarkers/blood , Case-Control Studies , Female , Humans , Intercellular Signaling Peptides and Proteins/blood , Male , RANK Ligand/blood
8.
Aging Clin Exp Res ; 30(11): 1327-1333, 2018 Nov.
Article in English | MEDLINE | ID: mdl-29476481

ABSTRACT

BACKGROUND: Blood pressure variability (BPV) may have prognostic implications for cardiovascular risk and cognitive decline; however, BPV has yet to be studied in old and very old people. AIMS: Aim of the present study was to evaluate the extent of BPV and to identify variables associated with BPV among older subjects. METHODS: A retrospective study of patients aged ≥ 65 years who underwent 24-h ambulatory blood pressure monitoring (ABPM) was carried out. Three different BPV indexes were calculated for systolic and diastolic blood pressure (SBP and DBP): standard deviation (SD), coefficient of variation (CV), and average real variability (ARV). Demographic variables and use of antihypertensive medications were considered. RESULTS: The study included 738 patients. Mean age was 74.8 ± 6.8 years. Mean SBP and DBP SD were 20.5 ± 4.4 and 14.6 ± 3.4 mmHg. Mean SBP and DBP CV were 16 ± 3 and 20 ± 5%. Mean SBP and DBP ARV were 15.7 ± 3.9 and 11.8 ± 3.6 mmHg. At multivariate analysis older age, female sex and uncontrolled mean blood pressure were associated with both systolic and diastolic BPV indexes. The use of calcium channel blockers and alpha-adrenergic antagonists was associated with lower systolic and diastolic BPV indexes, respectively. CONCLUSIONS: Among elderly subjects undergoing 24-h ABPM, we observed remarkably high indexes of BPV, which were associated with older age, female sex, and uncontrolled blood pressure values.


Subject(s)
Blood Pressure Monitoring, Ambulatory/methods , Blood Pressure/physiology , Hypertension/physiopathology , Age Factors , Aged , Aged, 80 and over , Antihypertensive Agents/therapeutic use , Female , Humans , Male , Multivariate Analysis , Retrospective Studies , Sex Factors
9.
Int J Endocrinol ; 2017: 9839017, 2017.
Article in English | MEDLINE | ID: mdl-28751911

ABSTRACT

[This corrects the article DOI: 10.1155/2015/907689.].

10.
PLoS One ; 12(6): e0178463, 2017.
Article in English | MEDLINE | ID: mdl-28582403

ABSTRACT

The aim of this study was to evaluate differences in T helper cell sub-types and osteoclast (OCs) precursors in peripheral blood between patients affected by early rheumatoid arthritis (eRA) and healthy controls. The effect of administration of cholecalcipherol on clinical and laboratory parameters was subsequently evaluated, by a parallel, randomized double blind, placebo controlled trial. Thirty nine eRA patients and 31 age-matched controls were enrolled and compared for levels of 25OH vitamin D, T helper cell sub-types, OCs precursors including both classical and non-classical and pro-inflammatory cytokines at baseline. Eligible patients were female ≥18 years of age with a diagnosis of RA, as defined by the American College of Rheumatology 2010 criteria for <6 months prior to inclusion in the study. Patients with auto-immune or inflammatory diseases other than RA were excluded. Patients treated with glucocorticoids (GCs), disease modifying activity drugs and biologic agents within the past 6 months were also excluded. In the second phase of the study, eRA patients were randomly assigned to standard treatment with methotrexate (MTX) and GCs with (21) or without (18) cholecalcipherol (300,000 IU) and followed for 3 months; the randomization was done by computer generated tables to allocate treatments. Three patients didn't come back to the follow up visit for personal reasons. None of the patients experienced adverse events. The main outcome measures were T cells phenotypes, OCs precursors and inflammatory cytokines. Secondary outcome measure were clinical parameters. In eRA, 25OH vitamin D levels were significantly lower. CD4+/IFNγ+,CD4+/IL4+, CD4+/IL17A+ and CD4+IL17A+IFNγ+, cells were increased in eRA as well as non-classical OCs precursors, whereas T regulatory cells were not altered. TNFα, TGFß1, RANKL, IL-23 and IL-6 were increased in eRA. Non-classical OCs, IL-23 and IL-6 correlated with disease severity and activity. Standard treatment with MTX and GC ameliorated clinical symptoms and reduced IL-23, whereas it did not affect CD4+ cells sub-sets nor OCs precursors. After 3 months, the combined use of cholecalcipherol significantly ameliorated the effect of treatment on global health. In eRA, a significant imbalance in T CD4+ sub-types accompanied by increased levels of non-classical OCs precursors and pro-inflammatory cytokines was observed. A single dose of cholecalcipherol (300,000 IU) combined with standard treatment significantly ameliorates patients general health.


Subject(s)
Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Cholecalciferol/therapeutic use , Immunologic Factors/therapeutic use , Osteoclasts/drug effects , T-Lymphocytes, Helper-Inducer/drug effects , Adolescent , Adult , Age of Onset , Aged , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/pathology , Case-Control Studies , Cell Differentiation , Cytokines/biosynthesis , Cytokines/metabolism , Double-Blind Method , Female , Glucocorticoids/therapeutic use , Humans , Methotrexate/therapeutic use , Middle Aged , Osteoclasts/immunology , Osteoclasts/pathology , Severity of Illness Index , T-Lymphocytes, Helper-Inducer/immunology , T-Lymphocytes, Helper-Inducer/pathology , Treatment Outcome
11.
Aging Clin Exp Res ; 29(3): 491-497, 2017 Jun.
Article in English | MEDLINE | ID: mdl-27100358

ABSTRACT

BACKGROUND: Uncertainties about efficacy and safety of oral anticoagulant therapy (OAT) among older and frail medical patients with atrial fibrillation (AF) largely contribute to under-prescription of these drugs. AIMS: In this prospective observational cohort study, we investigated mortality, and ischemic and hemorrhagic events, in hospital-discharged older patients with AF. METHODS: Stroke and bleeding risk were evaluated using CHA2DS2-VASC and HAS-BLED scores. Comorbidity, frailty, cognitive and nutritional status and functional autonomy were evaluated using standardized scales. Independent associations between clinical variables, including OAT use, and all-cause mortality, fatal and non-fatal ischemic and hemorrhagic events, were evaluated. Further clinical outcomes comparison between patients treated with OAT and those untreated was performed after adjustment for significant differences in patient baseline characteristics with propensity score matching. RESULTS: Of 452 patients included (mean age 81.6 years, 54.9 % women, roughly 30 % cognitively impaired and/or functionally dependent, mean CHA2DS2-VASC and HAS-BLED scores 4.6 and 2.8, respectively), 151 (33.4 %) died during a mean follow-up period of 300.5 days; ischemic and hemorrhagic stroke occurred in 4.0 and 0.4 % of patients, respectively, and major bleedings in 6.2 %. DISCUSSION: After multivariate analysis, OAT at discharge was associated with lower overall mortality and reduced occurrence of ischemic stroke, the first finding being confirmed in propensity score matched analysis. CONCLUSIONS: Among older vulnerable AF patients with high post discharge death rate, OAT was associated, among other multiple factors, with reduced mortality and lower occurrence of ischemic stroke.


Subject(s)
Anticoagulants/therapeutic use , Atrial Fibrillation/complications , Stroke/mortality , Stroke/prevention & control , Administration, Oral , Aged , Aged, 80 and over , Anticoagulants/adverse effects , Comorbidity , Female , Hemorrhage/chemically induced , Humans , Incidence , Male , Middle Aged , Practice Patterns, Physicians' , Prospective Studies , Risk Assessment , Risk Factors , Stroke/etiology
12.
Am J Cardiol ; 117(4): 590-595, 2016 Feb 15.
Article in English | MEDLINE | ID: mdl-26718230

ABSTRACT

In this retrospective cohort observational study, we investigated mortality, ischemic, and hemorrhagic events in patients ≥65 years with atrial fibrillation consecutively discharged from an Acute Geriatric Ward in the period 2010 to 2013. Stroke and bleeding risk were evaluated using CHA2DS2-VASC (congestive heart failure/left ventricular dysfunction, hypertension, aged ≥75 years, diabetes mellitus, stroke/transient ischemic attack/systemic embolism, vascular disease, aged 65 to 74 years, gender category) and HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly) scores. Co-morbidity, cognitive status, and functional autonomy were evaluated using standardized scales. Independent associations among clinical variables, including use of vitamin K antagonist-based oral anticoagulant therapy (OAT), all-cause mortality, and fatal and nonfatal ischemic and hemorrhagic events, were evaluated. Further clinical outcomes comparison between patients treated with OAT and those untreated was performed after adjustment for significant differences in patient baseline characteristics with propensity score matching. Of 980 patients discharged (mean age 83 years, 60% women, roughly 30% cognitively impaired or functionally dependent, mean CHA2DS2-VASC and HAS-BLED scores 4.8 and 2.1, respectively), 505 (51.5%) died during a mean follow-up period of 571 days; ischemic and hemorrhagic stroke occurred in 82 (12.3%) and 13 patients (1.3%), respectively, and major bleedings in 43 patients (4.4%). Vitamin K antagonists' use was independently associated with reduced mortality (odds ratio 0.524) and with a nonsignificant reduction in incidence of ischemic stroke, without excess in bleeding risk. Similar findings were observed in the 2 propensity score-matched cohorts of patients. In conclusion, among vulnerable patients with atrial fibrillation ≥65 years with high post-discharge death rate, OAT was associated, among other multiple factors, with reduced mortality.


Subject(s)
Anticoagulants/administration & dosage , Atrial Fibrillation/drug therapy , Brain Ischemia/epidemiology , Geriatric Assessment/methods , Hemorrhage/epidemiology , Inpatients , Aged , Aged, 80 and over , Anticoagulants/adverse effects , Atrial Fibrillation/mortality , Brain Ischemia/etiology , Female , Follow-Up Studies , Hemorrhage/chemically induced , Humans , Incidence , Italy/epidemiology , Male , Retrospective Studies , Risk Factors , Survival Rate/trends
13.
Geriatr Gerontol Int ; 16(3): 314-21, 2016 Mar.
Article in English | MEDLINE | ID: mdl-25752922

ABSTRACT

AIM: To characterize elderly medical patients and identify factors associated with prolonged length of stay. METHODS: The present prospective observational study evaluated consecutive patients aged ≥65 years admitted in acute geriatric and medical wards. A comprehensive assessment including demographic, clinical, functional and cognitive variables was carried out. Delayed discharge was defined when patients were discharged later than the date they were deemed medically ready for discharge by physicians. The analysis was initially carried out on the total sample and subsequently according to whether hospital admission had been from home, or from intermediate or long-term facilities. RESULTS: Among 1568 patients (age 81.3 ± 7.3 years, 712 men), we observed a high prevalence of functional dependence, cognitive impairment, chronic immobilization and frailty (50%, 25%, 20% and 40%, respectively). Overall, delayed discharge occurred in 442 cases - resulting in 2637 days of prolonged hospital stay - and was independently associated with impairment in activities of daily living, frailty, high comorbidity and inappropriate admission. Among patients admitted from home (roughly 90% of the sample), delayed discharge occurred in 392 patients, and was independently associated with cognitive impairment, functional dependence, low severity of comorbidity and inappropriate admission (OR 3.39). Among patients admitted from intermediate or long-term facilities, lower cognitive impairment and greater severity of functional dependence were independently associated with prolonged stay. CONCLUSIONS: Poor health conditions and high prevalence of geriatric syndromes are extremely common among older medical inpatients. Delayed discharge was mainly observed in patients admitted from home, and associated with cognitive impairment (OR 1.12) and functional dependence (OR 1.49).


Subject(s)
Geriatric Assessment , Hospitalization , Length of Stay/statistics & numerical data , Aged , Aged, 80 and over , Female , Humans , Male , Prospective Studies
14.
Cell Metab ; 22(5): 799-810, 2015 Nov 03.
Article in English | MEDLINE | ID: mdl-26456334

ABSTRACT

Primary hyperparathyroidism (PHPT) is a common cause of bone loss that is modeled by continuous PTH (cPTH) infusion. Here we show that the inflammatory cytokine IL-17A is upregulated by PHPT in humans and cPTH in mice. In humans, IL-17A is normalized by parathyroidectomy. In mice, treatment with anti-IL-17A antibody and silencing of IL-17A receptor IL-17RA prevent cPTH-induced osteocytic and osteoblastic RANKL production and bone loss. Mechanistically, cPTH stimulates conventional T cell production of TNFα (TNF), which increases the differentiation of IL-17A-producing Th17 cells via TNF receptor 1 (TNFR1) signaling in CD4(+) cells. Moreover, cPTH enhances the sensitivity of naive CD4(+) cells to TNF via GαS/cAMP/Ca(2+) signaling. Accordingly, conditional deletion of GαS in CD4(+) cells and treatment with the calcium channel blocker diltiazem prevents Th17 cell expansion and blocks cPTH-induced bone loss. Neutralization of IL-17A and calcium channel blockers may thus represent novel therapeutic strategies for hyperparathyroidism.


Subject(s)
Bone Diseases, Metabolic/metabolism , Hyperparathyroidism, Primary/metabolism , Interleukin-17/metabolism , Animals , Bone Diseases, Metabolic/drug therapy , Bone Diseases, Metabolic/etiology , Bone Diseases, Metabolic/pathology , Calcium Channel Blockers/therapeutic use , Humans , Hyperparathyroidism, Primary/complications , Hyperparathyroidism, Primary/drug therapy , Hyperparathyroidism, Primary/pathology , Interleukin-17/biosynthesis , Mice , Receptors, Tumor Necrosis Factor, Type I/biosynthesis , Signal Transduction , T-Lymphocytes/metabolism , T-Lymphocytes/pathology , Tumor Necrosis Factor-alpha/biosynthesis
15.
Int J Endocrinol ; 2015: 907689, 2015.
Article in English | MEDLINE | ID: mdl-26457082

ABSTRACT

Osteoporosis is now recognized as an important public health problem in elderly men as fragility fractures are complicated by increased morbidity, mortality, and social costs. This review comprises an overview of recent findings in pathophysiology, diagnosis, and treatment of male osteoporosis, with particular regard to the old population.

16.
Bone ; 76: 177-84, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25827255

ABSTRACT

We investigated the effect of bone turnover on glucose homeostasis, fat distribution and adipokine production during anabolic treatment with PTH. This is a parallel, randomized controlled, open label, trial. The randomization was done by computer generated tables to allocate treatments. Forty-six postmenopausal osteoporotic non-diabetic women were assigned to treatment with calcium and colecalcipherol with (24) or without (22) PTH 1-84. Patients were recalled after 3, 6, 12 and 18 months of treatment and markers of bone turnover, glucose metabolism, adipokine secretion and fat distribution were analyzed. Markers of bone turnover and adipokines were measured by ELISA. Glucose metabolism was evaluated by an oral glucose load test and insulin resistance and secretion were calculated. Fat and lean mass were evaluated by anthropometric measures. The effect of treatment on measured variables was analyzed by repeated measure test, and its effect on glucose was also evaluated by mediation analysis after correction for possible confounders. Twenty patients in the calcium and vitamin D groups and 19 in the group treated with PTH 1-84 completed the study. There were no significance adverse events. Treatment with PTH increases osteocalcin, both total (OC) and undercarboxylated (uOC), and decreases blood glucose, without influence on insulin secretion, resistance and pancreatic ß cell function. Treatment with PTH does not influence fat distribution and adipokine production. The results of the mediation analyses suggest a total effect of PTH on blood glucose, moderately mediated by OC and to a less extent by uOC. Here we suggest that treatment with PTH influences glucose metabolism partially through its effect on bone turnover, without influence on insulin secretion, resistance, pancreatic ß cell function and fat mass.


Subject(s)
Blood Glucose/analysis , Osteoporosis, Postmenopausal/drug therapy , Parathyroid Hormone/therapeutic use , Adipose Tissue/drug effects , Aged , Female , Humans , Middle Aged , Osteoporosis, Postmenopausal/blood
17.
Radiol Med ; 120(7): 674-82, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25652156

ABSTRACT

PURPOSE: The aim of this study was to investigate whether the population differences in osteoporosis observed nowadays is a reflection of the times and modern lifestyle factors, or whether they were also present in the past. MATERIALS AND METHODS: The study was performed on the skeletal remains of medieval and post-medieval populations from a burial ground in the North-West of Italy. Some individuals had been buried inside the church (privileged subjects), others outside in the parvis (members of rural population), and others still to the north of the church. X-ray, computed tomography and dual-energy X-ray absorptiometry studies were carried out on the lumbar spines and/or femurs of 27 male and 28 female individuals to determine any associations between cortical index, bone mineral density (BMD), gender, age and social status. RESULTS: No statistically significant differences were observed in cortical index values according to gender, age or place of burial. Conversely, statistically significant differences in average BMD values were observed according to place of burial; in particular, among those buried inside the church, a lower BMD was observed compared to the parvis group (1.09 vs. 1.42, p < 0.001) and the north group (1.09 vs. 1.49, p < 0.001). CONCLUSIONS: The differences observed in the BMD values may be related to the different lifestyle of the rural population, i.e. more dietary calcium intake, more sun exposure and vigorous physical activity, compared to that of the privileged individuals.


Subject(s)
Osteoporosis/history , Absorptiometry, Photon , Cadaver , Female , History, Medieval , Humans , Italy , Male , Osteoporosis/diagnostic imaging , Tomography, X-Ray Computed
18.
BMC Clin Pathol ; 14(1): 11, 2014 Mar 21.
Article in English | MEDLINE | ID: mdl-24655661

ABSTRACT

BACKGROUND: Dickoppf-1 (DKK-1) is a negative regulator of bone formation with tumorigenic potential. The up-regulation of DKK-1 is an early event in prostate cancer (PCa) development, thus we investigated its role as a marker in the diagnosis and prognosis of PCa. METHODS: We retrospectively enrolled 159 patients who underwent prostate biopsy, either for elevated PSA or suspect digital rectal examination, between 2003 and 2010. During the biopsy, one serum sample was collected from all patients; PSA and DKK-1 were measured by ELISA technique. Amongst the biopsy of 159 patients 75 were affected by PCa and 84 were not the mean period of follow-up for these patients was 5 years; a new biopsy was performed in case of PCa suspicion. RESULTS: PSA performed better than DKK-1 in detecting PCa (0.63 vs 0.51 respectively). Differently from PSA DKK-1 was significantly higher in patients who developed PCa during follow-up than in cancer-free ones, thus DKK-1 performed better than PSA in detecting these patients (0.67 vs 0.55). DKK-1 was significantly lower in patients with bone metastases, whereas PSA was not significantly different in patients with different outcomes. CONCLUSIONS: DKK-1 might be predictive for patients negative at first biopsy who will develop PCa and in the prognosis of bone metastases. It performed worse than PSA in the early diagnosis of Pca.

19.
Expert Opin Pharmacother ; 14(7): 949-56, 2013 May.
Article in English | MEDLINE | ID: mdl-23521229

ABSTRACT

INTRODUCTION: Osteoporosis is a common disease characterized by the occurrence of fragility fractures. Major osteoporotic fractures are associated with decreased quality of life and high costs. AREAS COVERED: This review summarizes clinical data on raloxifene (RLX), a second generation selective estrogen-receptor modulator (SERM), currently approved for the treatment of postmenopausal osteoporosis. RLX has estrogen effects on bone and lipid profile, whereas it has anti-estrogen effects on uterus and breast cells. Its main side effects are hot flushes and venous thromboembolism. Literature searches were conducted to retrieve articles reporting RLX clinical trial data. For comparison of safety and efficacy, post-marketing studies on RLX were included. EXPERT OPINION: RLX is effective in reducing vertebral fracture risk in osteoporotic women, it is safe and its ability to prevent breast cancer has to be considered in the analyses of cost/effect and of the ideal candidate to this treatment. RLX has to be avoided in patients with previous history of venous thromboembolism.


Subject(s)
Bone Density Conservation Agents/therapeutic use , Osteoporosis, Postmenopausal/drug therapy , Raloxifene Hydrochloride/therapeutic use , Bone Density Conservation Agents/adverse effects , Bone Density Conservation Agents/pharmacology , Breast Neoplasms/prevention & control , Clinical Trials as Topic , Cost-Benefit Analysis , Female , Humans , Osteoporotic Fractures/prevention & control , Raloxifene Hydrochloride/adverse effects , Raloxifene Hydrochloride/pharmacology , Selective Estrogen Receptor Modulators , Spinal Fractures/prevention & control
20.
Calcif Tissue Int ; 92(5): 437-43, 2013 May.
Article in English | MEDLINE | ID: mdl-23334353

ABSTRACT

We report the prevalence of osteoporosis, osteopenia, and fractures in a cohort of Italian women randomly recruited among the general population and validate the use of clinical guidelines in referring women for bone density testing. We enrolled in the study 995 healthy women (age range 45-92 years). A bone density test at the lumbar spine and femur was performed and a questionnaire on osteoporosis risk factors completed for all patients. The prevalence of osteoporosis was 33.67 %, that of osteopenia was 46.63, and 19.7 % were normal at bone density testing. Osteoporotic women were generally older and thinner, with a shorter period of estrogen exposure. The prevalence of fractures was 21.9 %, and fractured women had a lower bone density, were older, and had a longer postmenopausal period. Clinical guidelines for referring women for bone density testing performed poorly (the best performance was 68 %). This is the first study providing data on the prevalence of osteoporosis/osteopenia and of fractures in a cohort of healthy postmenopausal women. Known risk factors influence bone density and risk of fractures. The role of screening in detecting women with postmenopausal osteoporosis is far from optimal.


Subject(s)
Bone Density , Bone Diseases, Metabolic/pathology , Bone and Bones/pathology , Densitometry/methods , Osteoporosis, Postmenopausal/epidemiology , Aged , Aged, 80 and over , Decision Making , Decision Support Systems, Clinical , Estrogens/metabolism , Female , Humans , Italy/epidemiology , Middle Aged , Prevalence , Referral and Consultation , Risk Factors
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