Publications (246)569.17 Total impact
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Article: Common susceptibility alleles and SQSTM1 mutations predict disease extent and severity in a multinational study of patients with Paget's disease.
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ABSTRACT: BACKGROUND: Paget's disease of bone (PDB) has a strong genetic component. Here we investigated possible associations between genetic variants that predispose to PDB and disease severity. METHODS: Allelic variants identified as predictors of PDB from genome wide association studies were analysed in 1940 PDB patients from the UK, Italy, Western Australia and Spain. A cumulative risk allele score was constructed by adding the variants together and related to markers of disease severity, alone and in combination with SQSTM1 mutations. RESULTS: In SQSTM1 negative patients, risk allele scores in the highest tertile were associated with a 27% increase in disease extent, compared with the lowest tertile (p < 0.00001) with intermediate values in the middle tertile (20% increase; p = 0.0007). The effects were similar for disease severity score which was 15% (p = 0.01) and 25% (p < 0.00001) higher in the middle and upper tertiles, respectively. Risk allele score remained a significant predictor of extent and severity when SQSTM1 positive individuals were included, with an effect size approximately one-third of that observed with SQSTM1 mutations. A genetic risk score was developed by combining information from both markers, which identified subgroups of individuals with low, medium and high levels severity with a specificity of 70% and sensitivity of 55%. CONCLUSIONS: Risk allele scores and SQSTM1 mutations both predict extent and severity of PDB. It is possible that with further refinement, genetic profiling may be of clinical value in identifying individuals at high risk of severe disease who might benefit from enhanced surveillance and early intervention.Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 05/2013; · 6.04 Impact Factor -
Article: The future of pharmacogenetics for osteoporosis.
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ABSTRACT: The possibility to predict the outcome of medical treatments, both in terms of efficacy and development of adverse effects, is the main goal of modern personalized medicine. The principal aim of pharmacogenetics is to design specific predictive genetic tests, to be performed prior to any drug treatment, and to tailor the therapy for each patient based on the results of these tests. Few pharmacogenetic tests are today validated and commonly applied in clinical practice, and none in the area of osteoporosis and bone disorders. Surely, the complex regulation of bone metabolism and the involvement of numerous different molecular pathways makes it difficult to individuate responsible genes and polymorphisms involved in the modulation of anti-osteoporotic drug response and, subsequently, in designing specific predictive analyses.Pharmacogenomics 04/2013; 14(6):641-53. · 3.97 Impact Factor -
Article: Can fibroblast growth factor (FGF)-23 circulating levels suggest coronary artery abnormalities in children with Kawasaki disease?
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ABSTRACT: OBJECTIVES: Kawasaki disease (KD) is an acute self-limited panvasculitis, primarily affecting young children, with an outstanding risk of cardiovascular complications. Fibroblast Growth Factor-23 (FGF23) is the latest member of the FGF family, acting on phosphate metabolism, which has been shown to display a potential role in the vascular remodelling. The aim of our study was to test the hypothesis that circulating serum levels of FGF23 might be related to the occurrence of coronary artery abnormalities (CAA) in children with KD. METHODS: Serum of 109 consecutive KD patients (median age 30.5 months) were collected for the evaluation of intact FGF23 by ELISA test. Sixty sex/age-matched healthy children were studied as controls, after having excluded rheumatic, endocrinological and chronic renal diseases. In all these subjects a familiar predisposition to atherosclerosis was excluded. RESULTS: FGF23 levels resulted significantly higher in patients with KD than in controls (72±40 pg/ml vs. 12.3±3.2 pg/ml; p=0.01). Twenty-eight/109 KD patients having developed CAA (aneurysms or dilatations) presented significantly higher FGF23 levels than those without any coronary artery damage (120±40 pg/ml vs. 38.2±5 pg/ml; p<0.0001). Multiple logistic regression analysis showed that only serum FGF23 levels, among different general clinical and biochemical variables, were suggestive of coronary artery damage (OR=4.86). CONCLUSIONS: Based on this preliminary investigation, high serum FGF23 levels would seem suggestive of the potential occurrence of cardiac vascular complications in children with KD.Clinical and experimental rheumatology 01/2013; · 2.15 Impact Factor -
Article: Genetic predictors of skeletal outcomes in healthy fertile women: The Bonturno Study.
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ABSTRACT: Skeletal traits as height (Ht) or bone mineral density (BMD) are strongly inherited. Low-density lipoprotein receptor-related protein 5 (LRP5) and farnesyl diphosphonate synthase (FDPS) are candidate genes for bone phenotypes. From Bonturno study, we genotyped 570 healthy Caucasian women aged 20 to 50 years (yrs) for LRP5 rs4988321 (A/G) and rs3736228 (C/T) and FDPS rs2297480 (A/C) single nucleotide polymorphisms. Serum C-telopeptide of type I collagen (CTX), osteocalcin (OC), and N-terminal propeptide of type I procollagen (P1NP) were measured in BMD-evaluated subjects at lumbar spine (LS), total hip (TH) and femoral neck (FN) sites. LRP5 rs4988321 locus correlated with FN-BMD (P=0.0230), while LRP5 rs3736228 genotypes differed in LS-BMD (P=0.0428). When clustered by age, lower FN-BMD was detected in LRP5 GG (P=0.030) subjects of 41 to 50 years but not in younger. Both LRP5 GG and CC genotypes showed higher age-adjusted values of OC, CTX and P1NP. Increased CTX values were in LRP5 GGCC subjects than in those having at least one LRP5 A plus T alleles (P=0.0190). LRP5 CC, GG or GGCC subjects with at least one FDPS C allele showed higher levels of CTX and OC in 31 to 40 yrs or older subjects. In conclusion, LRP5 and FDPS loci age-specifically affect skeletal traits in healthy fertile women.Joint, bone, spine: revue du rhumatisme 12/2012; · 2.25 Impact Factor -
Article: When the government actively faces the burden of osteoporosis: the Italian experience.
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ABSTRACT: EPIDEMIOLOGY AND COSTS OF FRAGILITY FRACTURES IN ITALY: The problem of osteoporosis is emerging as growing phenomenon, with an enormous impact on quality of life and on health expenses. As a consequence, a reduction in the social and health impact of bone fragility would be associated with an improved quality of life of all elderly citizens and with valuable cost savings at the health system level. OSTEOPOROSIS: EVOLUTION OF THE CONCEPT IN ITALY: In the last 20 years, there have been enormous advances in the knowledge of diagnostic and therapeutic options and thus we would be in the position of starting effective therapies in at risk populations. However, this not always happens. NEW APPROACHES TO THE FRAGILITY FRACTURES BY THE ITALIAN GOVERNMENT: In this paper we offer to the reader the possibility to know the history of osteoporosis, its diagnosis and its therapy in Italy, a country where life expectancy is one of the highest in the world. THE FUTURE OF OSTEOPOROSIS IN ITALY: We hope that the example of Italy would serve as an inspiration to those countries where the history of osteoporosis only recently began.Archives of Osteoporosis 12/2012; 7(1-2):21-4. -
Article: Role of GSH/GSSG redox couple in osteogenic activity and osteoclastogenic markers of human osteoblast-like SaOS-2 cells.
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ABSTRACT: This study carries out in human osteoblast-like SaOS-2 cells a comprehensive analysis of glutathione ((1) GSH) redox system during osteogenic differentiation. For the first time a clear relationship between the expression of specific factors involved in bone remodelling and the changes of GSH/ oxidized GSH (GSSG) redox couple induced during the early phases of differentiation and mineralization process is found. The findings show that the time course of differentiation is characterized by a decrease in GSH/GSSG ratio, and this behavior is also related to the expression of osteoclastogenic markers. The maintenance of a high level of this ratio due to GSH exposure in the early phase of this process increases mRNA levels of osteogenic differentiation markers and the mineralization. Conversely, these events are decreased by a low GSH/GSSG ratio in a reversible manner. A redox regulation of runt-related transcription factor-2 (RUNX-2) activation through its phosphorylation is shown. An inverse relation between RUNX-2 activation and extracellular signal-regulated kinases (ERKs) related to GSH redox potential is observed. The GSH/GSSG redox couple affects also osteoclastogenesis mainly through osteoprotegerin (OPG) down expression with increase in receptor activator of nuclear factor-κB ligand (RANKL)/OPG ratio and viceversa. No redox regulation in RANKL expression is found. These results indicate that GSH/GSSG redox couple may have a pivotal role in bone remodeling and in bone redox-dysregulated diseases. Thereafter, they suggest the use of compounds able to modulate therapeutically not just GSH level but intracellular redox system through GSH/GSSG redox couple. © 2012 The Authors Journal compilation © 2012 FEBS.FEBS Journal 11/2012; · 3.79 Impact Factor -
Article: The burden of breast cancer in Italy: mastectomies and quadrantectomies performed between 2001 and 2008 based on nationwide hospital discharge records.
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ABSTRACT: BACKGROUND: Where population coverage is limited, the exclusive use of Cancer Registries might limit ascertainment of incident cancer cases. We explored the potentials of Nationwide hospital discharge records (NHDRs) to capture incident breast cancer cases in Italy. METHODS: We analyzed NHDRs for mastectomies and quadrantectomies performed between 2001 and 2008. The average annual percentage change (AAPC) and related 95% Confidence Interval (CI) in the actual number of mastectomies and quadrantectomies performed during the study period were computed for the full sample and for subgroups defined by age, surgical procedure, macro-area and singular Region. Re-admissions of the same patients were separately presented. RESULTS: The overall number of mastectomies decreased, with an AAPC of -2.1% (-2.3 -1.8). This result was largely driven by the values observed for women in the 45 to 64 and 65 to 74 age subgroups (-3.0%, -3.4 -3.6 and -3.3%, -3.8 -2.8, respectively). We observed no significant reduction in mastectomies for women in the remaining age groups. Quadrantectomies showed an overall +4.7 AAPC (95%CI:4.5--4.9), with no substantial differences by age. Analyses by geographical area showed a remarkable decrease in mastectomies, with inter-regional discrepancies possibly depending upon variability in mammography screening coverage and adherence. Quadrantectomies significantly increased, with Southern Regions presenting the highest average rates. Data on repeat admissions within a year revealed a total number of 46,610 major breast surgeries between 2001 and 2008, with an overall +3.2% AAPC (95%CI:2.8-3.6). CONCLUSIONS: In Italy, NHDRs might represent a valuable supplemental data source to integrate Cancer Registries in cancer surveillance.Journal of Experimental & Clinical Cancer Research 11/2012; 31(1):96. · 2.15 Impact Factor -
Article: Adherence to Calcium and Vitamin D supplementations: results from the ADVICE Survey.
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ABSTRACT: The ADVICE (ADherence in VItamin-D and Calcium Embedded or not) survey was aimed to evaluate the effect of a patient-focused motivation strategy on the adherence to calcium and vitamin D supplementation. The survey also intended to identify possible factors being able to influence the compliance (i.e. the existence of individual preferences towards different dosages or regimens of supplementation). We planned to involve consecutive patients visited between 2010 and 2011 at 35 centres specialized in diagnosis and treatment of osteoporosis in different Italian regions. Each patient has been requested to declare if he/she was already assuming any supplementation with calcium and vitamin D (naïve or not naïve). All patients underwent a first visit (T0) and two follow up visits at 6 and 12 months (T6 e T12). The assessment of the adherence was measured through the Morinsky Medication Adherence Scale, a score based on 8 different questions, specifically validated to determine therapeutical compliance (0-5: not acceptable; 6-7: acceptable; 8: ideal). 732 women (mean age: 66.9; average BMI: 25.3) and 30 men (mean age: 71.9; average BMI: 24.5) were enrolled; 34% of female patients (n=245) and 66% of males (n=20) reported previous fractures. Not naïve patients were 385 (54%). A total of 309 patients (43%) were concurrently assuming an antifracture drug; 229 subjects were osteoporotic (45%), while 224 were osteopenic (44%). The mean Morinsky score in not naïve patients was 5.72, 6.19 and 6.18 at T0, T6, and T12, respectively. Thus, no differences in the Morinsky score were observed between T6 and T12. Naïve patients showed an average Morinsky score of 5.78 at T6 and 6.39 at T12. Older age was not significantly associated with the observed changes in the scores. The onset of AEs related to the supplementation with calcium and vitamin D was able to negatively influence the adherence at the subsequent control point. Bone mineral density, previous fractures, and concurrent assumption of any antifracture drug did not significantly influence the adherence, as well as the differences in the dosages or regimens of calcium and vitamin D administration. Activities aimed to strengthen motivation of the patients improved the adherence to calcium and vitamin D supplementations after only 6 months.Clinical Cases in Mineral and Bone Metabolism 09/2012; 9(3):157-60. -
Dataset: A novel polymorphism at the GNAS1 gene associated
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Dataset: A Polymorphic CYP19 TTTA Repeat Influences Aromatase Activity and Estrogen Levels in Elderly Men Effects on Bone Metabolism -- Gennari et al 89 (6) 2803 -- Journal of Clinical Endocrinology & Metabolism
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Dataset: Azidothymidine Induces Apoptosis and Inhibits Cell Growth and
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Dataset: Biological effects of various regimes of 25-hydroxyvitamin
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Dataset: Analysis of estrogen receptor (ERα and ERβ) and BR
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Dataset: Allelic Loss in Parathyroid Tumors from Individuals
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Dataset: Calcium Bioavailability From a Calcium-Rich Mineral Water,
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Dataset: Calcium agonists in
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Dataset: DNA based Test When and Why to apply it to Primary Hyperparathyroidism Clinical
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Dataset: DNA-based test when and why to apply it to primary
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Dataset: ENDOCRINE RELATED CANCER FalchettiBrandi
Top co-authors
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Institutions
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1993–2013
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University of Florence
- • Dipartimento di Medicina Sperimentale e Clinica
- • Dipartimento di Scienze Biomediche, Sperimentali e Cliniche
Florence, Tuscany, Italy
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2012
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Sapienza University of Rome
- Department of Clinical and Molecular Medicine
Roma, Latium, Italy
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2011
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University of Rome Tor Vergata
Roma, Latium, Italy
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2004–2009
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Università di Pisa
Pisa, Tuscany, Italy -
Mayo Foundation for Medical Education and Research
- Division of Endocrinology, Diabetes, Metabolism, and Nutrition
Scottsdale, AZ, USA
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2008
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Aarhus Universitetshospital
Århus, Central Jutland, Denmark
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2006
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Erasmus MC
Rotterdam, South Holland, Netherlands -
The University of Edinburgh
- Rheumatic Diseases Unit
Edinburgh, SCT, United Kingdom
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2002
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Università Vita-Salute San Raffaele
Milano, Lombardy, Italy
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