Association of vitamin D and bisphenol A levels with cardiovascular risk in an elderly Italian population: results from the InCHIANTI study.

Few studies have evaluated the association between circulating levels of 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D), and the endocrine disruptor bisphenol A (BPA), with risk of cardiovascular (CV) disease in elderly individuals. This was a cross-sectional study in a subgroup of elderly people from the InCHIANTI Biobank in Italy. We examined the association between circulating serum vitamin D metabolites, 1,25(OH)2D, 25(OH)D, and the endocrine disrupting agent BPA, with an arbitrary CV risk score and the European Society of Cardiology-based 10-year CV risk (SCORE2/SCORE2-OP) using univariate and multiple regression. In 299 individuals, blood samples were tested for serum values of 25(OH)D, 1,25(OH)2D and urinary BPA levels. One hundred eighty individuals (60.2%) were deficient (< 20 ng/ml) in 25(OH)D. Levels of 25(OH)D and 1,25(OH)2D were negatively correlated with CV risk score (p < 0.0001 for both) as well as SCORE2/SCORE2-OP (p < 0.0001 for both) while BPA levels were positively correlated with both CV risk scores (p < 0.0001 for both). In a logistic regression model, male gender (odds ratio; OR: 2.1, 95% CI:1.1-3.8, p = 0.022), obesity (OR:2.8, 95% CI:1.2-6.5, p = 0.016) and BPA levels ≥ 110 ng/dl (OR:20.9, 95% CI:9.4-46.8, p < 0.0001) were associated with deficient levels of 25(OH)D. 1,25(OH)2D levels < 41 ng/dl and 25(OH)D levels < 20 ng/ml were associated with CV risk score ≥ 3 (OR: 4.16, 95% CI: 2.32-7.4, p < 0.0001 and OR: 1.86, 95% CI: 1.02-3.39, p = 0.044) respectively and 1,25(OH)2D levels < 41 ng/dl were associated with SCORE2/SCORE2-OP of ≥ 20% (OR:2.98, 95% CI: 1.7-5.2, p = 0.0001). In this cross-sectional analysis, BPA exposure was associated with significantly reduced levels of vitamin D that in turn were significantly associated with increased CV risk.

Hypoparathyroidism and pseudohypoparathyroidism in pregnancy: an Italian retrospective observational study.

BACKGROUND: Hypoparathyroidism (HypoPT) or pseudo-hypoparathyroidism (pseudo-HypoPT) during pregnancy may cause maternal and fetal/neonatal complications. In this regard, only a few case reports or case series of pregnant or lactating women have been published. The purpose of this study was to describe clinical and biochemical course, pharmacological management, and potential adverse events during pregnancy and post-partum in pregnant women with HypoPT or pseudo-HypoPT. This was a retrospective, observational, multicenter, study involving nine Italian referral centers for endocrine diseases affiliated with the Italian Society of Endocrinology and involved in "Hypoparathyroidism Working Group". RESULTS: This study identified a cohort of 28 women (followed between 2005 and 2018) with HypoPT (n = 25, 84% postsurgical, 16% idiopathic/autoimmune) and pseudo-HypoPT (n = 3). In HypoPT women, the mean calcium carbonate dose tended to increase gradually from the first to third trimester (+ 12.6%) in pregnancy. This average increase in the third trimester was significantly greater compared to the pre-pregnancy period (p value = 0.03). However, analyzing the individual cases, in 44% the mean calcium dosage remained unchanged throughout gestation. Mean calcitriol doses tended to increase during pregnancy, with a statistically significant increase between the third trimester and the pre-pregnancy period (p value = 0.02). Nevertheless, analyzing the individual cases, in the third trimester most women with HypoPT (64%) maintained the same dosage of calcitriol compared to the first trimester. Both mean calcium carbonate and calcitriol doses tended to decrease from the third trimester to the post-partum six months. Most identified women (~ 70%) did not display maternal complications and (~ 90%) maintained mean serum albumin-corrected total calcium levels within the low-to-mid normal reference range (8.5 ± 0.8 mg/dl) during pregnancy. The main complications related to pregnancy period included: preterm birth (n = 3 HypoPT women), and history of miscarriages (n = 6 HypoPT women and n = 2 pseudo-HypoPT women). CONCLUSION: This study shows that mean serum albumin-corrected total calcium levels were carefully monitored during pregnancy and post-pregnancy, with limited evaluation of other biochemical parameters, such as serum phosphate, 24 h urinary calcium, 25-OH vitamin D, and creatinine clearance. To avoid complications in mothers affected by (HypoPT) or (pseudo-HypoPT) and offspring, intense biochemical, clinical and pharmacological monitoring during pregnancy and breastfeeding is highly recommended.

Chronic hypoparathyroidism and treatment with teriparatide.

PURPOSE: Chronic hypoparathyroidism is usually treated with calcium and active vitamin D metabolites or analogs, despite the fact that their chronic use can lead to long-term complications. The use of hormone replacement therapy with PTH peptides [teriparatide and rhPTH (1-84)] has therefore been proposed. The main purpose of this study was to investigate the efficacy of teriparatide dose at 20 µg once or twice daily, in order to maintain normocalcemia reducing standard treatment, in adult patients with chronic hypoparathyroidism not well controlled with conventional treatment. METHODS: The study was a Phase III, open-label, non-comparative, clinical investigation (study period: 3 months), at a tertiary care clinical research center. Thirty patients with chronic hypoparathyroidism were screened, and 12 started teriparatide. After the optimization phase (0-4 weeks), calcium and calcitriol supplements were progressively reduced, while teriparatide 20 µg once daily was administered (5-7 weeks), and then could be titrated up to 20 µg twice daily (7-17 weeks). The main outcome measures included serum and urinary biochemical exams and Rand 36-Item Short Form Health Survey. RESULTS: This study showed that teriparatide 20 µg once daily was insufficient to discontinue calcium and calcitriol supplements to maintain normal serum calcium concentrations. Conversely, for more than half of patients treated with teriparatide 20 µg twice daily, calcium and calcitriol administration was avoidable, but in some cases at the expense of serum calcium and phosphate oscillations. CONCLUSIONS: Since intervention trials evaluating the efficacy and safety of teriparatide in hypoparathyroid patients are not yet available, the routine use of this molecule poses some doubts.

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.

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.

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.

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.

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.

Ten years of hip fractures in Italy: For the first time a decreasing trend in elderly women.

AIM: To evaluate the hospitalization rate of femoral neck fractures in the elderly Italian population over ten years. METHODS: We analyzed national hospitalizations records collected at central level by the Ministry of Health from 2000 to 2009. Age- and sex-specific rates of fractures occurred at femoral neck in people ≥ 65 years old. We performed a sub-analysis over a three-year period (2007-2009), presenting data per five-year age groups, in order to evaluate the incidence of the hip fracture in the oldest population. RESULTS: We estimated a total of 839008 hospitalizations due to femoral neck fractures between 2000 and 2009 in people ≥ 65, with an overall increase of 29.8% over 10 years. The incidence per 10000 inhabitants remarkably increased in people ≥ 75, passing from 158.5 to 166.8 (+5.2%) and from 72.6 to 77.5 (+6.8%) over the ten-year period in women and men, respectively. The oldest age group (people > 85 years old) accounted for more than 42% of total hospital admissions in 2009 (n = 39000), despite representing only 2.5% of the Italian population. Particularly, women aged > 85 accounted for 30.8% of total fractures, although they represented just 1.8% of the general population. The results of this analysis indicate that the incidence of hip fractures progressively increased from 2000 to 2009, but a reduction can be observed for the first time in women ≤ 75 (-7.9% between 2004 and 2009). CONCLUSION: Incidence of hip fractures in Italy are continuously increasing, although women aged 65-74 years old started showing a decreasing trend.

The role of the orthopaedic surgeon in the prevention of refracture in patients treated surgically for fragility hip and vertebral fracture.

UNLABELLED: THE ROLE OF THE ORTHOPAEDIC SURGEON IN THE TREATMENT OF PATIENTS WITH FRAGILITY FRACTURES IS TWOFOLD: the conservative or surgical treatment of the fracture, and the prevention of further fractures, establishing diagnostic and therapeutic procedures for osteoporosis. We evaluated 72 patients treated surgically for fragility vertebral fracture and 801 patients treated surgically for fragility hip fracture, operated from 2009 to 2010 at O.U. Orthopaedics and Traumatology of S.M. Annunziata Hospital of Florence, that have followed a treatment for refractures prevention according to the TARGET (Appropriate Treatment for Refractures GEriatric in Tuscany) Project of Tuscany Region. The average follow-up was 34 months. Patients with vertebral fracture treated for refractures prevention were 58 (80.6%), while patients with hip fracture treated for refractures prevention were 307 (38.3). RESULTS: the number of patients with vertebral fracture who had a refracture in the first two years after surgery was 12 (16.6%), of which 9 patients were not treated for osteoporosis. The percentage of refracture at 1 year after surgery in patients with hip fractures was 3.19% in 2009 and 2.17% in 2010, compared to 5.16% of refracture of 2006 when the TARGET Project was not yet started. Mortality at 1 year after surgery in patients with hip fracture treated for osteoporosis was 19% compared to 25-31% in the patients not treated for osteoporosis.

COL1A1 Sp1 variation and bone phenotypes in an Italian population.

BACKGROUND: Osteoporosis is the most common metabolic bone disorder of the elderly, affecting the normal bone turnover with an increased bone resorption and subsequent higher risk of fragility fractures. Collagen type 1 is the most represented protein in bone matrix. A genetic variation (Sp1) in intron 1 of COL1A1 gene has been associated to modulation of expression of the alpha 1 chain of collagen type 1 and it is considered a candidate polymorphism for predisposition to osteoporosis status and fragility fractures. Association studies, in ethnically different populations, are needed to strongly confirm the role of this polymorphism in bone metabolism. MATERIALS AND METHODS: We enrolled over 2,000 Italian individuals and studied their bone mineral density (BMD) and fractures in relation to age, sex and body mass index (BMI). Moreover, we analyzed the distribution of Sp1 polymorphism in these individuals and associated it to normal bone status, osteopenic condition or osteoporosis diagnosis, BMD and the presence of low-trauma fractures. RESULTS: The most rare ss genotype showed a trend for osteoporosis diagnosis with respect to both normal and osteopenic status. The same genotype resulted to be associated to lower values of BMD both at spine and femur sites. No association was found with fractures. DISCUSSION: In conclusion the presence of the homozygote ss genotype seemed to predispose to osteoporosis diagnosis and to be more frequent in subjects with lower spine and femur BMD values.

Antifracture drugs consumption in Tuscany Region before the Target Project: a valuable model for the analysis of administrative database.

OBJECTIVES: As the Target Project of Tuscany Region is aimed to identify significant changes occurring during the time of the project compared to the previous years, we have analyzed antifracture drugs consumption in the years immediately preceding the start-up of the program. METHODS: We have analyzed the regional administrative database to search for antifracture drugs delivered by the regional healthcare system to people living in Tuscany in the year 2009. Both drugs directly distributed by hospitals or local health authorities (direct distribution dataset, FED), and those delivered through pharmacies (pharmaceutical distribution dataset, SPF) were included in the analysis. Private expenditures were indirectly computed because total pharmaceutical expenditures were also known. A specific subgroup analysis has been carried out on elderly patients with femoral fractures (years 2006-2010), which represent the population of Target Project, in order to assess the evolution of all antifracture drug prescriptions before the start up of the project. RESULTS: A total of 690,768 boxes of antifracture drugs (20 million defined daily doses, DDD) have been delivered in year 2009 for total expenditures of 23 million Euros. Public expenditures accounted for 71% of the total (16 million; 6% of regional pharmaceutical expenditures). Alendronate and risedronate were the most used drugs. The number of antifracture medications prescribed within the first 90 days to elderly people with hip fractures increased in the period before the start-up of the Target project but they remained under 14%. CONCLUSIONS: There is the need for an appropriate management of antifracture therapies, as they represent a valuable proportion of pharmaceutical expenditures. This need is pointed out also by the remarkable amount of direct private expenditures and by the few number of hip fractured people starting a treatment.

Connections between the outcomes of osteoporotic hip fractures and depression, delirium or dementia in elderly patients: rationale and preliminary data from the CODE study.

BACKGROUND: osteoporosis, depression and other neuro-psychiatric disorders are very common after 50 years of age. Although these conditions recognize several and specific etiologic factors, they however appear to share physiologic, environmental processes and risk factors which may explain their possible association. METHODS: we have built up a specific research project (the CODE study, Connections between the outcomes of osteoporotic hip fractures and depression, delirium or dementia in elderly patients), and carried out a preliminary survey on 55 hip fractured elderly patients (42 women, mean age 85 years old and 13 men, mean age 82 years old), hospitalized at SS. Annunziata hospital in Florence from July to September 2010. RESULTS: there was a significant difference (p=0.010) in the functional recovery after surgery (as measured by Cumulated Ambulation Score, CAS) between depressed and non-depressed subjects (n=38), with a worse recovery and a lower CAS score in depressed patients (n=17). We also observed a higher prevalence of depression in the osteoporotic-fragile elderly people (69,1% of total sample). CONCLUSION: our preliminary survey has validated the suitability of the CODE study protocol in assessing connections between outcomes of osteoporotic hip fractures and depression in elderly patients, fostering the extension of the study (and suggesting also the inclusion of delirium and dementia) within a multicentric prospective study aimed to provide specific information and guidelines for osteoporotic fractured patients with concomitant depression or other neuro-psychiatric disorders.

Compliance to antifracture treatments in Tuscany: a regional survey based on institutional pharmaceutical dataset.

OBJECTIVE: compliance to any antifracture therapy is the most important parameter affecting the effectiveness of the treatment. The aim of this study was to evaluate patients compliance to antifracture therapies in the whole Tuscany population who benefit from treatments reimbursed by the Regional Healthcare System. METHODS: we have analyzed all antifracture drug prescriptions recorded in Tuscany regional pharmaceutical database concerning year 2009, from both in-hospital distribution database (direct drug delivery, FED), and private pharmacies across the whole region (SPF). Patients who started the treatment in 2008 and those continuing it in 2010 were also considered in the analysis. The sample size consisted in 92,250 people (1:9 male to female ratio). Compliance to antifracture treatments at 3, 6, 9, and 12 months was analyzed by single drug (using the defined daily dose, DDD), and by age group (40-50, 50-60, 60-70, 70-80, 90-100 years). RESULTS: patients compliance decreased under 80% after the first 3 months of treatment, reaching no more than 50% at 1 year. Our results show that compliance to antifracture treatments reflects the age of the patients. People aged 70-80 years old represent the age group most frequently treated with antifracture therapies (36.57% of total prescriptions), with alendronic acid being the most prescribed drug (29.73% of total drug prescribed). Monthly dosing did not increase compliance if compared to oral weekly regimens, while daily oral or s.c. dosing were associated to lower compliance rates. CONCLUSION: serious efforts need to be implemented to foster patients motivation in assuming their antifracture treatments for at least one year.