Maria Luisa Brandi

University of Florence, Florens, Tuscany, Italy

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Publications (670)2077.92 Total impact

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    ABSTRACT: Primary hyperparathyroidism is the main endocrinopathy associated with Multiple Endocrine Neoplasia type 1 syndrome. Cinacalcet is a calcimimetic agent licensed for the treatment of secondary hyperparathyroidism in patients with end-stage renal disease, and for the reduction of marked hypercalcemia in patients with parathyroid carcinoma and sporadic hyperparathyroidism requiring surgery but for whom parathyroidectomy is contraindicated. It may provide a medical alternative for the management of primary hyperparathyroidism in subjects affected by Multiple Endocrine Neoplasia type 1. In this longitudinal, intervention study, 33 MEN1 patients had been enrolled, 10 males and 23 females with a mean age of 40 ± 11.9 years, range 20-63. Primary hyperparathyroidism was the first clinical manifestation in 12 patients. All subjects commenced with Cinacalcet 30 mg/day, 22 patients starting therapy with calcimimetics as an alternative to surgery, and 11 patients opting for the medication after the onset of persistent post-surgical primary hyperparathyroidism. Duration of follow-up was 12 months. The results of this study show significant reductions in serum calcium. The changes in hormonal secretions of pituitary and gastroenteropancreatic glands were not significant, demonstrating the overall safety of this drug in this disease. Cinacalcet has been well tolerated by 28 patients, whereas five individuals complained of heartburn and grade 1 nausea, which did not prevent the completion of the study. In conclusion, Cinacalcet has resulted to be well tolerated and safe in patients with MEN1 syndrome and the calcium homeostasis was stabilized.
    Endocrine 07/2015; DOI:10.1007/s12020-015-0696-5 · 3.53 Impact Factor
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    ABSTRACT: Parathyroid hormone (PTH) is important in the assessment of calcium metabolism disorders. However, there are few data regarding PTH levels in childhood and adolescence. The aim of this study was to determine PTH levels in a large group of healthy children and adolescents. We retrospectively evaluated PTH levels in 1,580 healthy Caucasian children and adolescents (849 females, 731 males, aged 2.0-17.2 years) with 25-hydroxyvitamin D [25(OH)D] levels ≥30 ng/ml. All subjects with genetic, endocrine, hepatic, renal, or other known diseases were excluded. The serum intact PTH concentration (median and inter-quartile range) was 23.00 (15.00-31.60) pg/ml. In our population, the mean 25(OH)D value was 34.27 ± 4.12 ng/ml. The median PTH concentration in boys was 23.00 (15.00-32.00) pg/ml, whereas in girls it was 23.10 (15.00-31.10) pg/ml. However, in girls, PTH levels significantly increased in the age group of 8.1-10.0 years compared to the age group of 2.1-4.0 years (p < 0.0001), whereas in boys it significantly increased in the age groups of 10.1-12.0 years (p < 0.0001) and 12.1-14.0 years (p < 0.0001), leading to the hypothesis of a relationship between PTH level and pubertal and bone growth spurts. PTH levels in healthy children and adolescents covered a narrower range than the adult values. Obtaining reference values of PTH in childhood and adolescence could aid in the estimation of appropriate values of bone metabolites. © 2015 S. Karger AG, Basel.
    Hormone Research in Paediatrics 06/2015; DOI:10.1159/000432399 · 1.71 Impact Factor
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    ABSTRACT: Commonly, health behaviour theories have been applied to single behaviours, giving insights into specific behaviours but providing little knowledge on how individuals pursue an overall healthy lifestyle. In the context of diet and physical activity, we investigated the extent to which cross-behaviour cognitions, namely transfer cognitions and compensatory health beliefs, contribute to single behaviour theory. A total of 767 participants from two European regions (i.e., Germany n = 351, southern Europe n = 416) completed online questionnaires on physical activity and healthy dietary behaviour, behaviour-specific cognitions (i.e., self-efficacy, outcome expectancies, risk perception, intention, action planning, action control), as well as cross-behaviour cognitions, namely transfer cognitions and compensatory health beliefs. Nested path models were specified to investigate the importance of cross-behaviour cognitions over and above behaviour-specific predictors of physical activity and healthy nutrition. Across both health behaviours, transfer cognitions were positively associated with intention and self-regulatory strategies. Compensatory health beliefs were negatively associated with intention. Action planning and action control mediated the effect of intentions on behaviour. Cross-behaviour cognitions contribute to single behaviour theory and may explain how individuals regulate more than one health behaviour. Statement of contribution What is already known on this subject? Cross-behaviour cognitions are related to a healthy lifestyle. Compensatory health beliefs hinder the adoption of a healthy lifestyle. Transfer cognitions encourage the engagement in a healthy lifestyle. What does this study add? Transfer cognitions were positively associated with intentions, action planning, and action control over and above behaviour-specific cognitions. Compensatory health beliefs were related to intentions only. Both facilitating and debilitating cross-behaviour cognitions need to be studied within a unified multiple behaviour research framework. © 2015 The British Psychological Society.
    British Journal of Health Psychology 06/2015; DOI:10.1111/bjhp.12144 · 2.70 Impact Factor
  • L Cianferotti · A R Gomes · S Fabbri · A Tanini · M L Brandi
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    ABSTRACT: The calcium-sensing receptor (CaSR), a key player in the maintenance of calcium homeostasis, can influence bone modeling and remodeling by directly acting on bone cells, as demonstrated by in vivo and in vitro evidence. The modulation of CaSR signaling can play a role in bone anabolism. The calcium-sensing receptor (CaSR) is a key player in the maintenance of calcium homeostasis through the regulation of PTH secretion and calcium homeostasis, thus indirectly influencing bone metabolism. In addition to this role, in vitro and in vivo evidence points to direct effects of CaSR in bone modeling and remodeling. In addition, the activation of the CaSR is one of the anabolic mechanisms implicated in the action of strontium ranelate, to reduce fracture risk. This review is based upon the acquisition of data from a PubMed enquiry using the terms "calcium sensing receptor," "CaSR" AND "bone remodeling," "bone modeling," "bone turnover," "osteoblast," "osteoclast," "osteocyte," "chondrocyte," "bone marrow," "calcilytics," "calcimimetics," "strontium," "osteoporosis," "skeletal homeostasis," and "bone metabolism." A fully functional CaSR is expressed in osteoblasts and osteoclasts, so that these cells are able to sense changes in the extracellular calcium and as a result modulate their behavior. CaSR agonists (calcimimetics) or antagonists (calcilytics) have the potential to indirectly influence skeletal homeostasis through the modulation of PTH secretion by the parathyroid glands. The bone anabolic effect of strontium ranelate, a divalent cation used as a treatment for postmenopausal and male osteoporosis, might be explained, at least in part, by the activation of CaSR in bone cells. Calcium released in the bone microenvironment during remodeling is a major factor in regulating bone cells. Osteoblast and osteoclast proliferation, differentiation, and apoptosis are influenced by local extracellular calcium concentration. Thus, the calcium-sensing properties of skeletal cells can be exploited in order to modulate bone turnover and can explain the bone anabolic effects of agents developed and employed to revert osteoporosis.
    Osteoporosis International 06/2015; DOI:10.1007/s00198-015-3203-1 · 4.17 Impact Factor
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    ABSTRACT: Osteoarthritis (OA), a disease affecting different patient phenotypes, appears as an optimal candidate for personalized healthcare. The aim of the discussions of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) working group was to explore the value of markers of different sources in defining different phenotypes of patients with OA. The ESCEO organized a series of meetings to explore the possibility of identifying patients who would most benefit from treatment for OA, on the basis of recent data and expert opinion. In the first meeting, patient phenotypes were identified according to the number of affected joints, biomechanical factors, and the presence of lesions in the subchondral bone. In the second meeting, summarized in the present article, the working group explored other markers involved in OA. Profiles of patients may be defined according to their level of pain, functional limitation, and presence of coexistent chronic conditions including frailty status. A considerable amount of data suggests that magnetic resonance imaging may also assist in delineating different phenotypes of patients with OA. Among multiple biochemical biomarkers identified, none is sufficiently validated and recognized to identify patients who should be treated. Considerable efforts are also being made to identify genetic and epigenetic factors involved in OA, but results are still limited. The many potential biomarkers that could be used as potential stratifiers are promising, but more research is needed to characterize and qualify the existing biomarkers and to identify new candidates.
    06/2015; DOI:10.1007/s40266-015-0276-7
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    DESCRIPTION: The Tuscany Region was the first Italian Region to initiate a program for the prevention of hip fractures in over 65 year old. The T.A.R.Ge.T. project “Appropriate treatment of geriatric re-fractures in Tuscany” (Trattamento Appropriato delle Rifratture Geriatriche in Toscana), which is still on-going, includes a preliminary phase (2009-2010) for baseline analysis and education of the participating centers and a 4-year- prospective phase (2011-2014). The monitoring system is performed horizontally analyzing 5 different flows: SDO (Performance Hospitalization), SPF (Pharmaceutical Distribution Dataset), FED (Direct Distribution Dataset), SAA (Registry of Patients), SPA (Specialized Outpatient) flows. In this review will be shown some of the most important results of analyzes of the retrospective phase. Between 2006 and 2011 only 26% of hip fractured patients has being treated with anti-osteoporotic drugs. The percentage of treatment increases 10% after the second fracture. Until 2011 there wasn’t in Tuscany a prevention program of bone fragility; patients were treated with specific treatment only in severe cases: this phenomenon implies that mortality and re-fracture are higher on treated patients than in patients who did not have any kind of treatment. The treated patients are the most severe and therefore they have a higher risk of death and re-fracture. .
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    ABSTRACT: This article reports a taxonomic classification of rare skeletal diseases based on metabolic phenotypes. It was prepared by The Skeletal Rare Diseases Working Group of the International Osteoporosis Foundation (IOF) and includes 116 OMIM phenotypes with 86 affected genes. Rare skeletal metabolic diseases comprise a group of diseases commonly associated with severe clinical consequences. In recent years, the description of the clinical phenotypes and radiographic features of several genetic bone disorders was paralleled by the discovery of key molecular pathways involved in the regulation of bone and mineral metabolism. Including this information in the description and classification of rare skeletal diseases may improve the recognition and management of affected patients. IOF recognized this need and formed a Skeletal Rare Diseases Working Group (SRD-WG) of basic and clinical scientists who developed a taxonomy of rare skeletal diseases based on their metabolic pathogenesis. This taxonomy of rare genetic metabolic bone disorders (RGMBDs) comprises 116 OMIM phenotypes, with 86 affected genes related to bone and mineral homeostasis. The diseases were divided into four major groups, namely, disorders due to altered osteoclast, osteoblast, or osteocyte activity; disorders due to altered bone matrix proteins; disorders due to altered bone microenvironmental regulators; and disorders due to deranged calciotropic hormonal activity. This article provides the first comprehensive taxonomy of rare metabolic skeletal diseases based on deranged metabolic activity. This classification will help in the development of common and shared diagnostic and therapeutic pathways for these patients and also in the creation of international registries of rare skeletal diseases, the first step for the development of genetic tests based on next generation sequencing and for performing large intervention trials to assess efficacy of orphan drugs.
    Osteoporosis International 06/2015; DOI:10.1007/s00198-015-3188-9 · 4.17 Impact Factor
  • L Cianferotti · S Parri · G Gronchi · C Rizzuti · C Fossi · D M Black · M L Brandi
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    ABSTRACT: Scientific interest in vitamin D has greatly risen during the last 10 years. The analysis of the changes in vitamin D prescriptions and related costs in a regional prescription dataset has revealed a profound increase in the period 2006-2013. Further studies on cost-effectiveness of such increase in vitamin D supplementation are needed. The aim of this study was to analyze the changes in population-based prescription patterns of vitamin D supplements in the general population in an Italian regional setting during an 8-year period (2006-2013). Data have been retrieved from the database of reimbursed prescriptions of the Region of Tuscany containing all of the medical reimbursements for the whole regional population (total of 3,619,872 and 3,692,828 inhabitants in 2006 and 2013, respectively). Data referring to adult population (age 20-90+ years) have been considered for this analysis (3,033,530 in 2006 and 3,066,741 in 2013). Two different flows (pharmaceutical distribution dataset and general data flow) were taken into account, using the ATC5 coding system for vitamin D supplements alone or in combination with calcium or alendronate. The number of boxes dispensed was retrieved, the number of patients receiving a specific treatment was calculated, and a cost analysis was performed. An upsurge in the prescriptions of vitamin D compounds was disclosed, mainly sustained by a 75.3-fold increase in cholecalciferol, in all age groups and both sexes. This occurred in parallel to a 4.3-fold rise in prescriptions of oral alendronate in combination with cholecalciferol, a slight decrease in dispensed alendronate alone, and a modest increase in the prescription of the combination of calcium salts and cholecalciferol, and calcium alone. The total cost for reimbursement by the Regional Health System for vitamin D-related compounds rose from 3,242,100 euros in 2006 to 8,155,778 in 2013. The huge increase in vitamin D prescriptions and related costs in the last decade, as revealed by the analysis of a regional pharmaceutical dataset, reflects the increased awareness of the possible consequences of a poor vitamin D status. Further studies on cost-effectiveness of such increase in vitamin D supplementation are needed.
    Osteoporosis International 06/2015; DOI:10.1007/s00198-015-3187-x · 4.17 Impact Factor
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    ABSTRACT: Hypophosphatemic rickets (HR) is a rare disease that includes a group of hereditary and sporadic conditions characterized by renal phosphate loss associated with normal to low vitamin D serum concentration. The most common form is the X-linked hypophosphatemic rickets, with an incidence of 1: 20000. Several mutations have recently been identified in PHEX, FGF23, DMP1 and ENPP1 genes in patients with HR. Moreover, in vitro and in vivo studies suggested an involvement of MEPE for defective mineralization in HR. The present case series describes the clinical features and the analysis of genes implicated in HR in a cohort of 26 Italian HR patients. All patients were analyzed for PHEX and FGF23 genes by direct sequencing. When no mutations were detected, Multiplex Ligation-dependent Probe Amplification (MLPA) analysis was performed. The negative patients were screened for DMP1, MEPE and ENPP1 genes by direct sequencing. Twenty-two patients (84%) harbored mutations in PHEX gene. In particular, we detected 19 different mutations, 15 of which were novel. One patient presented a novel splice variation in ENPP1 gene while no alterations were identified in FGF23, DMP1 and MEPE genes. The genetic study of the families showed that 11 patients (55%) had de novo mutations. Clinical presentation and disease severity did not show an evident correlation between the mutation type. This report represents the first large familial study performed on Italian patients. It confirms that mutations in PHEX are the most frequent cause of HR. Furthermore, the variety of clinical manifestations identified in our HR patients underlines the extreme clinical and genetic heterogeneity of this disease. Copyright © 2015. Published by Elsevier Inc.
    Bone 06/2015; 79. DOI:10.1016/j.bone.2015.05.040 · 4.46 Impact Factor
  • Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):1224.3-1225. DOI:10.1136/annrheumdis-2015-eular.5804 · 10.38 Impact Factor
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    ABSTRACT: A care gap exists between the health care needs of older persons with fragility fractures and the therapeutic answers they receive. The Fracture Prevention Service (FPS), a tailored in-hospital model of care, may effectively bridge the osteoporosis care gap for hip-fractured older persons. The purpose of this study was to evaluate the efficacy of the FPS in targeting persons at high risk of future fracture and to improve their adherence to treatment. This was a prospective observational study conducted in a teaching hospital with traumatology and geriatric units, and had a pre-intervention and post-intervention phase. The records of 172 participants were evaluated in the pre-intervention phase, while data from 210 participants were gathered in the post-intervention phase. All participants underwent telephone follow-up at 12 months after hospital discharge. The participants were patients aged ≥65 years admitted to the orthopedic acute ward who underwent surgical repair of a proximal femoral fracture. A multidisciplinary integrated model of care was established. Dedicated pathways were implemented in clinical practice to optimize the identification of high-risk persons, improve their evaluation through bone mineral density testing and blood examinations, and initiate an appropriate treatment for secondary prevention of falls and fragility fractures. Compared with the pre-intervention phase, more hip-fractured persons received bone mineral density testing (47.62% versus 14.53%, P<0.0001), specific pharmacological treatments (48.51% versus 17.16%, P<0.0001), and an appointment for evaluation at a fall and fracture clinic (52.48% versus 2.37%, P<0.0001) in the post-intervention phase. Independent of some confounders, implementation of the FPS was positively associated with recommendations for secondary fracture prevention at discharge (P<0.0001) and with 1-year adherence to pharmacological treatment (P<0.0001). The FPS is an effective multidisciplinary integrated model of care to optimize identification of older persons at highest risk for fragility fracture, to improve their clinical management, and to increase adherence to prescriptions.
    Clinical Interventions in Aging 06/2015; 10:1035-1042. DOI:10.2147/CIA.S76695 · 1.82 Impact Factor
  • Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):529.2-530. DOI:10.1136/annrheumdis-2015-eular.1097 · 10.38 Impact Factor
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    ABSTRACT: Several compounds are produced along the complex pathways of vitamin D3 metabolism, and synthetic analogs have been generated to improve kinetics and/or vitamin D receptor activation. These metabolites display different chemical properties with respect to the parental or native vitamin D3, i.e., cholecalciferol, which has been, so far, the supplement most employed in the treatment of vitamin D inadequacy. Hydrophilic properties of vitamin D3 derivatives facilitate their intestinal absorption and their manageability in the case of intoxication because of the shorter half-life. Calcidiol is a more hydrophilic compound than parental vitamin D3. Active vitamin D analogs, capable of binding the vitamin D receptor evoking vitamin D-related biological effects, are mandatorily employed in hypoparathyroidism and kidney failure with impaired 1α-hydroxylation. They have been shown to increase BMD, supposedly ameliorating calcium absorption and/or directly affecting bone cells, although their use in these conditions is jeopardized by the development of hypercalciuria and mild hypercalcemia. Further studies are needed to assess their overall safety and effectiveness in the long-term and new intermittent regimens, especially when combined with the most effective antifracture agents.
    Endocrine 05/2015; DOI:10.1007/s12020-015-0606-x · 3.53 Impact Factor
  • Luisella Cianferotti · Caterina Fossi · Maria Luisa Brandi
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    ABSTRACT: Hip fractures are one of the most serious conditions in frail elderly subjects, greatly increasing morbidity and mortality, and decreasing healthy life years. Since their first introduction on the market, hip protectors have been revealed to be a potential preventive measure for hip fractures, in addition to other well-known recognized medical interventions and rehabilitation procedures. However, randomized controlled trials have given contradictory results regarding their efficacy. Moreover, little data are available on the cost effectiveness of hip protectors. Adherence is a major problem in assessing the effectiveness of hip protectors in preventing fractures. Indeed, there is a lack of general consensus on a standard definition and quantitative objective estimation of adherence to hip protectors, along with still scarce evidence on specific interventions on how to ameliorate it. From what is known so far, it seems reasonable to advise the use of hip protectors in aged care facilities, since recent pooled analyses have suggested their efficacy in this setting. The introduction of sensors combined with hip protectors will probably address this issue, both for monitoring and optimizing compliance, especially in elderly people. In the meantime, new, well-designed studies following specific guidelines are strongly encouraged and needed. In particular, studies in community-dwelling elderly individuals at high risk of first or further fragility fractures are required. The optimization of the tested devices in a preclinical setting according to international standard biomechanical testing is necessary.
    Calcified Tissue International 04/2015; 97(1). DOI:10.1007/s00223-015-0002-9 · 2.75 Impact Factor
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    ABSTRACT: Bone tissue engineering represents a challenge in regenerative medicine. Many types of materials have been studied as scaffolds in combination with mesenchymal stem cells, in order to develop viable substitutes able to restore and maintain the function of human bone tissues in skeletal defects. In this work, we have evaluated the viability, the adhesion and the proliferation of human adipose-derived stem cells (hADSCs) in association with poli(Ɛ-caprolactone), PCL, a biodegradable polyester, for future application in regenerative medicine. After the Local Ethical Committee approval, human adipose tissue was minced and digested at 37°C in 3 mg/ml collagenase type I, for three hours. Primary cells were cultured in growth medium (10% FBS, 1 ng/ml bFGF and 1% antibiotics) at 37°C and 5% CO2. Characterized hADSCs, (CD44+, CD105+, STRO1+ and CD45-), were plated on PCL film to evaluate fibronectin adhesion protein and cytoskeleton, by immunocytochemistry, using laser scanning confocal microscopy. Cell viability and proliferation were analyzed by Acridine Orange (AO) staining and MTT assay on days 2, 4, 7, 10, 13, 16 after cell seeding on PCL film at appropriate density (5 x 103). Statistical analysis was performed by linearity test. No qualitative differences were found in cell adhesion and cytoskeleton fiber morphology between hADSCs grown on PCL film and hADSCs grown on polystyrene, used as control. MTT assay has measured a consistent growth of absorbance during all the studied period for hADSCs seeded on PCL (linear regression r2= 0,86), suggesting that good cell viability was achieved on biomaterial. Cytocompatibility was also confirmed by AO staining microscopic observations. PCL construct has shown encouraging results in terms of cell adhesion and viability of hADSCs, opening new possibilities for future application in bone tissue engineering. Experiments are in progress in order to evaluate the osteogenic differentiation process of hADSCs on PCL. Acknowledgment This work was supported by Regione Toscana-POR CREO FESR 2007-2013.BANDO UNICO R&S 2012, linea A. Decreto dirigenziale n. 2746, 17/06/2014. Progetto REOSS.
    4th Joint Meeting of ECTS and IBMS; 04/2015
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    ABSTRACT: Human disorders of phosphate (Pi) handling and skeletal mineralization represent a group of rare bone diseases. One of these disease is tumoral calcinosis (TC). In this study, we present the case of a patient with TC with a new GALNT3 gene mutation. We also performed functional studies using an in vitro cellular model. Genomic DNA was extracted from peripheral blood collected from a teenage Caucasian girl affected by TC, and from her parents. A higher capability to form mineralization nodules in vitro was found in human preosteoblastic cells of mutant when compared to wild-type controls. We found a novel homozygous inactivating splice site mutation in intron I (c.516-2a>g). A higher capability to form mineralization nodules in vitro was found in the mutant cells in human preosteoblastic cells when compared to wild-type controls. Understanding the functional significance and molecular physiology of this novel mutation will help to define the role of FGF23 in the control of Pi homeostasis in normal and in pathological conditions.
    Calcified Tissue International 04/2015; 96(5). DOI:10.1007/s00223-015-9974-8 · 2.75 Impact Factor
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    ABSTRACT: IntroductionOver the last 50 years, the spectrum of clinical presentation of primary hyperparathyroidism (PHPT) has shifted from a symptomatic disorder, characterized by symptoms of hypercalcemia, nephrolithiasis, and overt bone disease, toward a less symptomatic or asymptomatic disorder [1]. The recognition of the asymptomatic variant of PHPT has markedly increased following the inclusion of serum calcium measurement in the multichannel biochemical screening.Parathyroidectomy (PTX) is the only definitive cure of PHPT. PTX is appropriate to consider in all patients with PHPT and should be recommended in patients with the symptomatic variant. The question of whether patients with asymptomatic PHPT should undergo surgery, as it is recommended in the symptomatic counterpart, has been the focus of four International Workshops. The latest has been held in Florence on September 19-21, 2013. The guidelines for surgery in patients with asymptomatic PHPT and monitoring for those who do not unde ...
    Journal of endocrinological investigation 03/2015; 38(5). DOI:10.1007/s40618-015-0261-3 · 1.55 Impact Factor
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    ABSTRACT: Abstract Despite the near concurrent publication by influential scientific organizations, there are important differences in interpretation of the evidence base and the conclusions derived from the recent Osteoarthritis Research Society International (OARSI) guidelines for the management of knee osteoarthritis, the American College of Rheumatology (ACR) (concerning also hip and hand osteoarthritis) and the algorithm recommendations by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). This is particularly evident for the drug class of Symptomatic Slow-Acting Drugs in OsteoArthritis. In this paper, we highlight these differences and try to understand where they derive from, proposing an evidence-based interpretation.
    Current Medical Research and Opinion 03/2015; 31(5):1-15. DOI:10.1185/03007995.2015.1027183 · 2.37 Impact Factor
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    ABSTRACT: Osteoarthritis is a syndrome affecting a variety of patient profiles. A European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis and the European Union Geriatric Medicine Society working meeting explored the possibility of identifying different patient profiles in osteoarthritis. The risk factors for the development of osteoarthritis include systemic factors (e.g., age, sex, obesity, genetics, race, and bone density) and local biomechanical factors (e.g., obesity, sport, joint injury, and muscle weakness); most also predict disease progression, particularly joint injury, malalignment, and synovitis/effusion. The characterization of patient profiles should help to better orientate research, facilitate trial design, and define which patients are the most likely to benefit from treatment. There are a number of profile candidates. Generalized, polyarticular osteoarthritis and local, monoarticular osteoarthritis appear to be two different profiles; the former is a feature of osteoarthritis co-morbid with inflammation or the metabolic syndrome, while the latter is more typical of post-trauma osteoarthritis, especially in cases with severe malalignment. Other biomechanical factors may also define profiles, such as joint malalignment, loss of meniscal function, and ligament injury. Early- and late-stage osteoarthritis appear as separate profiles, notably in terms of treatment response. Finally, there is evidence that there are two separate profiles related to lesions in the subchondral bone, which may determine benefit from bone-active treatments. Decisions on appropriate therapy should be made considering clinical presentation, underlying pathophysiology, and stage of disease. Identification of patient profiles may lead to more personalized healthcare, with more targeted treatment for osteoarthritis.
    Drugs & Aging 02/2015; 32(3). DOI:10.1007/s40266-015-0243-3 · 2.50 Impact Factor
  • Alessia Metozzi · Lorenzo Bonamassa · Gemma Brandi · Maria Luisa Brandi
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    ABSTRACT: Bone metabolism is regulated by the action of two skeletal cells: osteoblasts and osteoclasts. This process is controlled by many genetic, hormonal and lifestyle factors, but today more and more studies have allowed us to identify a neuronal regulation system termed ‘bone–brain crosstalk’, which highlights a direct relationship between bone tissue and the nervous system. The first documentation of an anatomic relationship between nerves and bone was made via a wood cut by Charles Estienne in Paris in 1545. His diagram demonstrated nerves entering and leaving the bones of a skeleton. Later, several studies were conducted on bone innervation and, as of today, many observations on the regulation of bone remodeling by neurons and neuropeptides that reside in the CNS have created a new research field, that is, neuroskeletal research.
    Expert Review of Endocrinology &amp Metabolism 02/2015; 10(2). DOI:10.1586/17446651.2015.979787

Publication Stats

14k Citations
2,077.92 Total Impact Points


  • 1982–2015
    • University of Florence
      • • Dipartimento di Chirurgia e Medicina Traslazionale (DCMT)
      • • Dipartimento di Scienze Biomediche, Sperimentali e Cliniche
      Florens, Tuscany, Italy
  • 2014
    • Euro Mediterranean Scientific and Biomedical Institute
      Brindisi, Apulia, Italy
  • 2013
    • Misericordia of Florence
      Florens, Tuscany, Italy
  • 2012–2013
    • Sapienza University of Rome
      • Department of Clinical and Molecular Medicine
      Roma, Latium, Italy
    • Santa Maria del Pozzo
      Napoli, Campania, Italy
    • Universitas Sriwijaya
      Palembang, South Sumatra, Indonesia
  • 2006–2010
    • Azienda Ospedaliero Universitaria Careggi
      • Department of Internal Medicine
      Firenzuola, Tuscany, Italy
    • Erasmus MC
      • Department of Internal Medicine
      Rotterdam, South Holland, Netherlands
  • 2007
    • Università di Pisa
      • Department of Clinical and Experimental Medicine
      Pisa, Tuscany, Italy
  • 2005–2007
    • Istituto Ortopedico Rizzoli
      • Laboratory for Orthopedic Pathophysiology and Regenerative Medicine
      Bolonia, Emilia-Romagna, Italy
  • 2002
    • Università Vita-Salute San Raffaele
      Milano, Lombardy, Italy
  • 1993–1998
    • Università degli studi di Parma
      • Dipartimento di Scienze Chirurgiche
      Parma, Emilia-Romagna, Italy
  • 1996
    • Università degli Studi di Siena
      • Department of Medicine, Surgery and Neuroscience
      Siena, Tuscany, Italy
  • 1995
    • William Harvey Research Institute
      Londinium, England, United Kingdom
    • University of Bologna
      Bolonia, Emilia-Romagna, Italy
  • 1994
    • University of Catania
      Catania, Sicily, Italy
  • 1987–1993
    • National Institutes of Health
      • • Branch of Metabolic Diseases Branch (MDB)
      • • Branch of Surgery
      • • Laboratory of Genetics (LG)
      베서스다, Maryland, United States
  • 1992
    • CRO Centro di Riferimento Oncologico di Aviano
      Aviano, Friuli Venezia Giulia, Italy
  • 1986–1989
    • The National Institute of Diabetes and Digestive and Kidney Diseases
      Maryland, United States
    • Northern Inyo Hospital
      BIH, California, United States