Osteomalacia Is Not a Single Disease.

Among bone-material qualities, mineralization is pivotal in conferring stiffness and toughness to the bone. Osteomalacia, a disease ensuing from inadequate mineralization of the skeleton, is caused by different processes leading to decreased available mineral (calcium and/or phosphate) or enzymatic alterations. Vitamin D deficiency, which remains the major cause of altered mineralization leading to inadequate intestinal calcium and phosphate absorption, may be also associated with other conditions primarily responsible for abnormal mineralization. Given the reality of widespread vitamin D inadequacy, a full biochemical assessment of mineral metabolism is always necessary to rule out or confirm other conditions. Both too-high or too-low serum alkaline phosphatase (ALP) levels are important for diagnosis. Osteomalacic syndrome is reversible, at least in part, by specific treatment. Osteomalacia and bone mineralization themselves constitute largely unexplored fields of research. The true prevalence of the different forms of osteomalacia and the recovery after proper therapy have yet to be determined in the real world. Although non-invasive techniques to assess bone mineralization are not available in clinical practice, the systematic assessment of bone quality could help in refining the diagnosis and guiding the treatment. This review summarizes what is known of osteomalacia recent therapeutic developments and highlights the future issues of research in this field.

Characterization of Skeletal Muscle Endocrine Control in an In Vitro Model of Myogenesis.

Skeletal muscle has remarkable regenerative abilities regulated by a highly orchestrated process involving the activation of cellular and molecular responses, which are dependent on satellite cells. These cells maintain the stem cell population and provide numerous myogenic cells that proliferate, differentiate, fuse and lead to new myofiber formation for a functional contractile tissue. We have isolated and characterized satellite cells obtained from human biopsies and established an in vitro model of myogenesis, evaluating muscle regeneration, monitoring the dynamic increases of the specific myogenic regulatory factors and the final formation of multinucleated myofibers. As the skeletal muscle is an endocrine tissue able of producing many substances that can act on distant organs, and it can be physiologically modulated by a variety of hormones, we embarked in a project of characterization of muscle cell endocrinology machinery. The expression of a large array of hormone receptors was quantified during the process of myogenesis. The results obtained showed a significant and generalized increase of all the tested hormone receptors along the process of differentiation of human cultured cells from myoblasts to myocytes. Interestingly, also the production of the myokine irisin increased in a parallel manner. These findings point to the human cultured myoblasts as an ideal model to characterize the skeletal muscle endocrine machinery and its hormonal regulation.

Evidence of a possible therapeutic role of vitamin D in a cohort of adult Caucasian vitiligo patients.

Reduced serum 25(OH)D levels have been largely reported in vitiligo, which is an autoimmune skin disorder characterized by the appearance of achromic macules. Since vitamin D can positively modulate immune function and stimulate melanogenesis in vitro, a possible role of sufficient vitamin D levels in promoting the stability of the disease and repigmentation process might be hypothesized in vitiligo. Hence, we conducted an observational study on medical records related to 101 vitiligo patients, in order to correlate baseline 25(OH)D levels with the baseline vitiligo activity and repigmentation of vitiligo macules on a 6-month follow-up. According to our results, at baseline we found that active vitiligo was significantly associated with 25(OH)D deficiency (≤20 ng/mL) (P = 0.036) or insufficiency (21-29 ng/mL) (P = 0.041), while stable disease was significantly associated with sufficient 25(OH)D levels (30-100 ng/mL) (P = 0.043). After 6 months, vitiligo patients with sufficient 25(OH)D levels (30-100 ng/mL) achieved a significantly higher degree of repigmentation. In conclusion, our study provides a novel evidence of a significant positive association of sufficient 25(OH)D levels with the stability of the disease and a satisfactory repigmentation process in Caucasian adult vitiligo patients and strengthen the need to assess vitamin D status in vitiligo. The correlation between sufficient vitamin D levels and a satisfactory course of the disease opens the way for future randomized controlled trials assessing a possible beneficial role of vitamin D supplementation on vitiligo.

Characterization of a novel CDC73 gene mutation in a hyperparathyrodism-jaw tumor patient affected by parathyroid carcinoma in the absence of somatic loss of heterozygosity.

Hyperparathyrodism-jaw tumor (HPT-JT) syndrome is an autosomal dominant disorder. Loss of function of the cell division cycle protein 73 homolog (CDC73) gene is responsible for the syndrome. This gene encodes an ubiquitously expressed 531 amino acid protein, parafibromin, that acts as a tumor suppressor. Loss of heterozygosity (LOH) of the CDC73 locus in many HPT-JT associated parathyroid tumors from patients with germline mutation is in accordance with Knudson's "two-hit" model for hereditary cancer. A 41-year-old man with mandible ossifying fibroma suffered from severe hypercalcemia due to parathyroid carcinoma (PC). Genetic analysis was performed to evaluate germinal and somatic CDC73 gene mutation as well as real-time qRT-PCR to quantify CDC73 mRNA, miR-155 and miR-664 expression levels. Immunohistochemistry and Western blotting (WB) assay were carried out to evaluate parafibromin protein expression. A novel heterozygous nonsense mutation, c.191-192 delT, was identified in the CDC73 gene. No CDC73 LOH was found in PC tissue, nor any differences in expression levels for CDC73 gene, miR-155 and miR-664 between PC and parathyroid adenoma control tissues. On the contrary, both immunohistochemistry and WB assay showed an approximate 90% reduction of parafibromin protein expression in PC. In conclusion, this study describes a novel germinal mutation, c.191-192 delT, in the CDC73 gene. Despite normal CDC73 gene expression, we found a significant decrease in parafibromin. We hypothesize that a gene silencing mechanism, possibly induced by microRNA, could play a role in determining somatic post-transcriptional inactivation of the wild type CDC73 allele.

Functional outcomes and mortality in geriatric and fragility hip fractures-results of an integrated, multidisciplinary model experienced by the "Florence hip fracture unit".

PURPOSE: The aim of this study was to evaluate the outcomes of an integrated multidisciplinary hip fracture unit through the following parameters: time to surgery, mortality, return to activities of daily living, adherence to re-fractures prevention programs. METHODS: Six hundred seventy-seven consecutive patients with hip fracture were included in the study. We calculated the time to surgery as the time in hours from admission until surgery. The in-hospital mortality was calculated as the number of deaths that occurred before discharge. Each patient was then evaluated post-operatively at six weeks, three months, and one year. We studied basic activity of daily living (BADL) and the New Mobility Scale (NMS). Adherence to re-fractures prevention programs was also evaluated. RESULTS: 88.9% of patients underwent surgery within two calendar days from admission. In-hospital mortality was 2.4%, and the overall mortality at one year from the intervention was 18.7%. Full mobility status or a low impairment of the mobility status was reached in 32.1% of the patients at one year and a level ≥ 3 of autonomy in BADL was reached in 62.4% (338/542) of patients. Three hundred forty-two patients were prescribed a specific therapy for secondary prevention of re-fracture. CONCLUSIONS: An integrated, multidisciplinary model for the treatment of hip fragility fractures was effective in reducing time to surgery and mortality, increasing the level autonomy and mobility status and promoting adherence to re-fracture therapy.

Prevalence of Chronic Hypoparathyroidism in a Mediterranean Region as Estimated by the Analysis of Anonymous Healthcare Database.

Epidemiological data on prevalence and incidence of chronic hypoparathyroidism are still scarce. This study aimed to establish prevalence of chronic hypoparathyroidism and incidence of surgical hypoparathyroidism using the analysis of electronic anonymous public health care database. Data referred to a 5-year period (2009-2013, Region of Tuscany, Italy, as a sample representative of the whole Mediterranean/European population, estimated mean population: 3,750,000 inhabitants) were retrieved by the analysis of pharmaceutical distribution dataset, containing data related to drugs reimbursed by public health system, hospital discharge and procedures codes, and ICD9 exemption codes for chronic diseases. The application of a specific algorithm was applied to indirectly identify people with chronic hypoparathyroidism as assuming chronic therapy with active vitamin D metabolites (AVDM). The number of people taking AVDM for a period equal to or longer than 6 months till the end of the study period, with ICD9 exemption code for hypoparathyroidism, and with a disease-related discharge code were identified. Within this restricted group, patients with chronic kidney disease and osteoporosis were excluded. The indirect estimate of chronic hypoparathyroidism in a European Mediterranean subpopulation by means of the analysis of chronic therapy with AVDM was 27/100,000 inhabitants (female:male ratio = 2.2:1), with a mean age of 63.5 ± 16.7 years. The risk of developing hypoparathyroidism after neck surgery was 1.5%. While the epidemiological approaches based on disease code and hospital discharge code greatly underestimates the prevalence of hypoparathyroidism, the indirect estimate of this disease through the analysis of prescriptions of AVDM in a European region is in line with the results of studies performed in other regions of the world.

HypoparaNet: A Database of Chronic Hypoparathyroidism Based on Expert Medical-Surgical Centers in Italy.

Hypoparathyroidism is a rare disease characterized by low serum calcium levels and absent or deficient parathyroid hormone level. Regarding the epidemiology of chronic hypoparathyroidism, there are limited data in Italy and worldwide. Therefore, the purpose of this study was to build a unique database of patients with chronic hypoparathyroidism, derived from the databases of 16 referral centers for endocrinological diseases, affiliated with the Italian Society of Endocrinology, and four centers for endocrine surgery with expertise in hypoparathyroidism, to conduct an epidemiological analysis of chronic hypoparathyroidism in Italy. The study was approved by the Institutional Review Board. A total of 537 patients with chronic hypoparathyroidism were identified. The leading etiology was represented by postsurgical hypoparathyroidism (67.6%), followed by idiopathic hypoparathyroidism (14.6%), syndromic forms of genetic hypoparathyroidism (11%), forms of defective PTH action (5.2%), non-syndromic forms of genetic hypoparathyroidism (0.9%), and, finally, other forms of acquired hypoparathyroidism, due to infiltrative diseases, copper or iron overload, or ionizing radiation exposure (0.7%). This study represents one of the first large-scale epidemiological assessments of chronic hypoparathyroidism based on data collected at medical and/or surgical centers with expertise in hypoparathyroidism in Italy. Although the study presents some limitations, it introduces the possibility of a large-scale national survey, with the final aim of defining not only the prevalence of chronic hypoparathyroidism in Italy, but also standards for clinical and therapeutic approaches.

The Epidemiology of Hypoparathyroidism in Italy: An 8-Year Register-Based Study.

Hypoparathyroidism is a rare endocrine disorder, but few studies have focused on the epidemiology and hospital management of the disease and none has been performed in Italy. We investigated the prevalence of different forms of hypoparathyroidism among hospitalized patients in Italy during an 8-year period. This study is designed as a retrospective register-based study. We retrieved data from the "Record of Hospital Discharge" (SDO) of the Italian Health Ministry, from the year 2006 to 2013 and analyzed the codes corresponding to hypoparathyroidism-related diagnoses. The inpatient prevalence of the disease was also calculated after excluding repeated hospitalizations. Overall, 27,692 hospitalization episodes for hypoparathyroidism were identified during the entire period (72.2% in women and 27.8% in men; mean age 49.5 ± 22.9 years). The mean length of stay was 7.4 ± 9.8 days (25.9% of the episodes requiring less than 3 days of stay). The mean hospitalization rate for hypoparathyroidism was 5.9/100,000 inhabitants per year and there was a significant decrease during the period of 2006-2013 (p < 0.0001). The mean hospitalization rate for postsurgical hypoparathyroidism was 1.4/100,000 inhabitants per year and the trend showed a significant reduction during the years (p < 0.0001). The mean prevalence of hypoparathyroidism among inpatients was 5.3/100,000 inhabitants per year, and there was a significant decrease over the years (p < 0.0001). Hypoparathyroidism, particularly the postsurgical form of the disease, is not an uncommon condition among hospitalized patients in Italy. We observed a tendency to a decrease in the frequency of hospitalization during the period 2006-2013.

Clinical guidelines for the prevention and treatment of osteoporosis: summary statements and recommendations from the Italian Society for Orthopaedics and Traumatology.

BACKGROUND: The Italian Society for Orthopaedics and Traumatology conceived this guidance-which is primarily addressed to Italian orthopedic surgeons, but should also prove useful to other bone specialists and to general practitioners-in order to improve the diagnosis, prevention, and treatment of osteoporosis and its consequences. MATERIALS AND METHODS: Literature reviews by a multidisciplinary team. RESULTS: The following topics are covered: the role of instrumental, metabolic, and genetic evaluations in the diagnosis of osteoporosis; appraisal of the risk of fracture and thresholds for intervention; general strategies for the prevention and treatment of osteoporosis (primary and secondary prevention); the pharmacologic treatment of osteoporosis; the setting and implementation of fracture liaison services for tertiary prevention. Grade A, B, and C recommendations are provided based on the main levels of evidence (1-3). Toolboxes for everyday clinical practice are provided. CONCLUSIONS: The first up-to-date Italian guidelines for the primary, secondary, and tertiary prevention of osteoporosis and osteoporotic fractures are presented.

Molecular genetics in primary hyperparathyroidism: the role of genetic tests in differential diagnosis, disease prevention strategy, and therapeutic planning. A 2017 update.

Primary hyperparathyroidism (PHPT) is one of the most frequent endocrine disease in developed countries. It mainly occurs as sporadic cases (about 90-95% of cases), while only the remaining 5-10% is represented by familial inherited parathyroid disorders due to causative mutations in specific target genes. Clinical variability among the different familial parathyroid syndromes is generally linked to the specific mutated gene and it can predispose subjects to different manifestations of parathyroid pathology, various degrees of PHPT severity, persistence and/or after-surgery recurrences. Genetic tests is helpful in differential diagnosis favouring the recognition of the specific familial PHPT syndrome and, subsequently, in planning the most suitable surgical procedures and/or pharmacological interventions. Moreover, genetic test is important to recognise mutation carriers, within PHPT familial forms, even before the appearance of biochemical and/or clinical symptoms. This review resumes general concepts about genetic diagnosis of PHPT in familial hereditary syndromes, specifically describing why, when, and which genetic screenings should be performed in every specific PHPT-associated parathyroid disease.

The use of cholecalciferol in patients with hip fracture.

INTRODUCTION: Major osteoporotic fractures are steadily increasing due to population aging. Programs of secondary prevention against refracture are essential to decrease morbidity and mortality and the cost for individuals and the society. Vitamin D supplementation and optimization of calcium intake are of a pivotal importance to start specific osteoporosis treatment and for its safety and efficacy. Cholecalciferol is the most widely employed drug for vitamin D supplementation. PURPOSE: Aim of this study was to assess the trends in the use of vitamin D supplements containing cholecalciferol in the population of hip fracture patients older than 65 years, resident in the region of Tuscany (Italy) in the years 2011-2015 and to describe vitamin D status in a subgroup of this individuals directly referred to a bone clinic for further evaluation after hip osteoporotic fracture. METHODS: Data were retrieved from the electronic anonymous regional administrative database administered by the Region of Tuscany (Italy) in the years 2011-2015 within the T.A.R.Ge.T. project (Trattamento Appropriato delle Rifratture Geriatriche in Toscana, i.e., "Appropriate treatment of geriatric refractures in Tuscany"), a program endorsed by the region itself. Data pertaining to cholecalciferol prescriptions and hospital discharge codes were retrieved and appropriately crossed to get data on the use of cholecalciferol supplements in patients before and after a hip fracture. A retrospective analysis was carried out in a subgroup of subjects (n 254) appropriately referred to the local fracture liaison service after the major osteoporotic fracture and vitamin D status in terms of serum 25(OH) vitamin D levels was assessed. RESULTS: The majority of subjects experiencing a hip fracture (98.2% and 88.3% in 2011 and 2015, respectively) did not receive vitamin D supplements at the time of the fracture event. Although a trend in increase in prescriptions for cholecalciferol supplements could be observed in the years of the study, the percentage of treated individuals remained low even after the fracture, since only 30-35% of subjects receives cholecalciferol supplements at one year after the fracture. Cholecalciferol remained the most prescribed drug in this population, while a substantial decrease of cholecalciferol in association with calcium salts was observed. The use of high doses of cholecalciferol has decreased in this population, while diminished the use of the drops has been accompanied by an increase in prescriptions of single monthly dose supplements. CONCLUSIONS: The correction of vitamin D inadequacy is preliminary to any treatment for osteoporosis and together with calcium may reduce fracture risk by itself. The prescription of vitamin D supplements is low in patients before and after a hip fracture in a Mediterranean region and despite the overall increase in vitamin use and abuse in the general population. Proper educational programs and active fracture liaison services are needed in order to bridge this gap.

The LARO-MEN1 study: a longitudinal clinical experience with octreotide Long-Acting Release in patients with Multiple Endocrine Neoplasia type 1 Syndrome.

Multiple endocrine neoplasia type 1 (MEN1) is a rare hereditary tumoral syndrome, featured by a combination of neoplasms of various endocrine and nonendocrine tissues. Approximately 33% of MEN1-related deaths are due to the malignant behaviour of well-differentiated neuroendocrine tumors (NETs), for which a preventive surgical treatment is not feasible. Somatostatin analogues (SSA) have been employed in the treatment of NETs in the stage of advanced or metastatic disease, in order to control the growth and secretion of tumor lesions. A longitudinal, open label study named "LARO-MEN1" was undertaken in order to assess whether early medical treatment with long-acting SSA could act as a preventive approach in small MEN1-related gastroenteropancreatic (GEP) NETs. Thirty consecutive patients affected by MEN1 were screened and 8 patients with small (<2 cm) NETs and abnormal laboratory values of at least one of the GEP hormones were administered octreotide acetate slow-release formulation (LAR) (10 mg i.m. every 28 days). Octreotide LAR was effective in decreasing GEP hormones and overall safe in the majority of patients up to six years of treatment, maintaining the disease stable also in terms of tumor size. The positive outcomes of this study in MEN1 patients reinforce the results obtained in advanced NETs on the use of SSA, opening to the opportunity for preventive use of octreotide LAR, aimed to delay or even avoid surgery in these patients.

Prevalence of osteoporosis in the Italian population and main risk factors: results of BoneTour Campaign.

BACKGROUND: BoneTour is a campaign conducted throughout the Italian territory for the assessment of Italian people bone status and for the prevention of osteoporosis. METHODS: A total of 7305 sequential subjects of both sexes were screened, collecting clinical data through the FRAX™ questionnaire, and measuring heel bone stiffness by Quantitative Ultrasonography (QUS). The 10-year risk for hip and major osteoporotic fractures was calculated taking into account personal or family history of fragility fracture, smoking, alcohol abuse, rheumatoid arthritis, prolonged steroids assumption. Additional risk factors were evaluated, including early menopause, poor sunlight exposure, low dietary calcium intake, physical inactivity, number of pregnancies, months of lactation, tobacco cigarettes smoked per year, specific causes of secondary osteoporosis. Through a correlation study, the influence of each factor on the development of osteoporosis was analyzed. RESULTS: As many as 18 % of women suffer from osteoporosis, as defined by QUS T-score. The calculation of FRAX™ confirmed the weight of the already known risk factors. The correlation study revealed the significance of some additional factors, such as hyperthyroidism, nephrolithiasis, Crohn disease, ulcerative colitis, celiac disease, poor sun exposure, and oophorectomy before age 50. CONCLUSIONS: The high prevalence of secondary osteoporosis in the Italian population clearly indicates the importance of additional risk factors not yet included in the FRAX™ algorithm, for which preventive measures should be considered. Screening campaigns may allow both early diagnosis and access to treatment.

Epigenetic Mechanisms in Bone Biology and Osteoporosis: Can They Drive Therapeutic Choices?

Osteoporosis is a complex multifactorial disorder of the skeleton. Genetic factors are important in determining peak bone mass and structure, as well as the predisposition to bone deterioration and fragility fractures. Nonetheless, genetic factors alone are not sufficient to explain osteoporosis development and fragility fracture occurrence. Indeed, epigenetic factors, representing a link between individual genetic aspects and environmental influences, are also strongly suspected to be involved in bone biology and osteoporosis. Recently, alterations in epigenetic mechanisms and their activity have been associated with aging. Also, bone metabolism has been demonstrated to be under the control of epigenetic mechanisms. Runt-related transcription factor 2 (RUNX2), the master transcription factor of osteoblast differentiation, has been shown to be regulated by histone deacetylases and microRNAs (miRNAs). Some miRNAs were also proven to have key roles in the regulation of Wnt signalling in osteoblastogenesis, and to be important for the positive or negative regulation of both osteoblast and osteoclast differentiation. Exogenous and environmental stimuli, influencing the functionality of epigenetic mechanisms involved in the regulation of bone metabolism, may contribute to the development of osteoporosis and other bone disorders, in synergy with genetic determinants. The progressive understanding of roles of epigenetic mechanisms in normal bone metabolism and in multifactorial bone disorders will be very helpful for a better comprehension of disease pathogenesis and translation of this information into clinical practice. A deep understanding of these mechanisms could help in the future tailoring of proper individual treatments, according to precision medicine's principles.

Hip Protectors: Are They Worth it?

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.

The T.A.R.Ge.T. project: a regional program to reduce hip fracture in elderly patients. Main results of retrospective phase.

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.

Habitual fish intake and clinically silent carotid atherosclerosis.

BACKGROUND: Fish consumption is recommended as part of a healthy diet. However, there is a paucity of data concerning the relation between fish consumption and carotid atherosclerosis. We investigated the association between habitual fish consumption and asymptomatic carotid atherosclerosis, defined as the presence of plaques and/or increased intima-media thickness (≥ 0.90 mm), in non-diabetic participants. METHODS: Nine hundred-sixty-one (range of age: 18-89 yrs; 37.1% males) adult participants without clinically known atherosclerotic disease were randomly recruited among the customers of a shopping mall in Palermo, Italy, and cross-sectionally investigated. Each participant answered a food frequency questionnaire and underwent high-resolution ultrasonographic evaluation of both carotid arteries. Routine laboratory blood measurements were obtained in a subsample of 507 participants. RESULTS: Based on habitual fish consumption, participants were divided into three groups: non-consumers or consumers of less than 1 serving a week (24.0%), consumers of 1 serving a week (38.8%), and consumers of ≥ 2 servings a week (37.2%). Age-adjusted prevalence of carotid atherosclerosis (presence of plaques or intima media thickness ≥ 0.9 mm) was higher in the low fish consumption group (13.3%, 12.1% and 6.6%, respectively; P = 0.003). Multivariate analysis evidenced that carotid atherosclerosis was significantly associated with age (OR = 1.12; 95% CI = 1.09-1.14), hypertension on pharmacologic treatment (OR = 1.81; 95% CI = 1.16-2.82), and pulse pressure (OR = 1.03; 95% CI = 1.01-1.04), while consuming ≥2 servings of fish weekly was protective compared with the condition of consumption of <1 serving of fish weekly (OR = 0.46; 95% CI = 0.26-0.80). CONCLUSIONS: High habitual fish consumption seems to be associated with less carotid atherosclerosis, though adequate interventional trials are necessary to confirm the role of fish consumption in prevention of cardiovascular disease.

Correlation between osteoporosis and cardiovascular disease.

Several evidences have shown in the last years a possible correlation between cardiovascular diseases and osteoporosis. Patients affected with osteoporosis, for example, have a higher risk of cardiovascular diseases than subjects with normal bone mass. However, the heterogeneous approaches and the different populations that have been studied so far have limited the strength of the findings. Studies conducted in animal models show that vascular calcification is a very complex mechanism that involves similar pathways described in the normal bone calcification. Proteins like BMP, osteopontin, osteoprotegerin play an important role at the bone level but are also highly expressed in the calcified vascular tissue. In particular, it seems that the OPG protect from vascular calcification and elevated levels have been found in patients with CVD. Other factors like oxidative stress, inflammation, free radicals, lipids metabolism are involved in this complex scenario. It is not a case that medications used for treating osteoporosis also inhibit the atherosclerotic process, acting on blood pressure and ventricular hypertrophy. Given the limited amount of available data, further studies are needed to elucidate the underlying mechanisms between osteoporosis and cardiovascular disease which may be important in the future also for preventive and therapeutic approaches of both conditions.

Vγ9Vδ2 T lymphocytes activation in osteoporotic patients treated with bisphosphonates.

Treatment with bisphosphonates induces differentiation and activation of Vγ9Vδ2 T lymphocytes obtained from peripheral blood showing also an antitumoral effect in both in vitro and in vivo models. Aim of the present study was to determine in vivo the effect of BPs treatment in patients affected with osteoporosis on Vγ9Vδ2 T lymphocytes. We have studied Vγ9Vδ2 T lymphocytes expansion and differentiation from PBMC obtained from osteoporotic patients treated with one of the following bisphosphonates zoledronate, alendronate, neridronate or risedronate. We have found that zoledronic acid, followed by alendronate was the most effective on reducing CM population (100%) and increasing TEM and TEMRA γδ population. Our results indicate that in vivo treatment with BPs induces Vγ9Vδ2 cells to mature toward the effector phenotype, which may induce more antiresorptive responses.

Organ Neuroprosthetics: Connecting Transplanted and Artificial Organs with the Nervous System.

Implantable neural interfaces with the central and peripheral nervous systems are currently used to restore sensory, motor, and cognitive functions in disabled people with very promising results. They have also been used to modulate autonomic activities to treat diseases such as diabetes or hypertension. Here, this study proposes to extend the use of these technologies to (re-)establish the connection between new (transplanted or artificial) organs and the nervous system in order to increase the long-term efficacy and the effective biointegration of these solutions. In this perspective paper, some clinically relevant applications of this approach are briefly described. Then, the choices that neural engineers must implement about the type, implantation location, and closed-loop control algorithms to successfully realize this approach are highlighted. It is believed that these new "organ neuroprostheses" are going to become more and more valuable and very effective solutions in the years to come.