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Purpose The main purpose of this study was to investigate the effects of 12 months of rhPTH (1–84) (Natpar®) treatment in a cohort of patients selected according to the indications of hypoparathyroidism guidelines. The use of recombinant human PTH (1–84) [rhPTH (1–84)] is approved as hormonal replacement therapy in patients with hypoparathyroidism not adequately controlled with conventional therapy. Methods It is a multicenter, observational, retro-prospective, open label study. Eleven Italian Endocrinological centers, members of Hypoparathyroidism Working Group of the Italian Society of Endocrinology (HypoparaNET) were involved. Main outcome measures were serum and urinary calcium and phosphate concentration, calcium-phosphate product, renal function, oral calcium and vitamin D doses, and clinical manifestations. Results Fourteen adult subjects, affected by chronic hypoparathyroidism, were treated with rhPTH (1–84) for 12 months. At 12 months of rhPTH (1–84) treatment, 61.5% of patients discontinued calcium supplement and 69.2% calcitriol. Mean albumin-adjusted total serum calcium levels quickly normalized after initiation of rhPTH (1–84) treatment compared to baseline (p = 0.009), remaining in the normal range until 12 months. Rare hypo-hypercalcemia episodes were reported. Renal function was maintained normal and no renal complications were reported. Serum and urinary phosphate and urinary calcium were maintained in the normal range. Mean phosphatemia levels linearly decreased from 3 months up to 12 months compared to baseline (p = 0.014). No severe adverse events were described. Conclusions Biochemical and clinical results confirm the efficacy and safety of rhPTH (1–84) therapy, which represents an important option for hypoparathyroid patients unresponsive to conventional therapy.

With regard to Dr. Wimalawansa’s comment [...]

In the recent years, both the prescriptions of serum 25(OH)D levels assay, and vitamin D supplementation are constantly increasing, as well as the costs to be incurred relating to these specific aspects. As in many other countries, the risk of vitamin D deficiency is particularly high in Italy, as recently confirmed by cohort studies in the general population as well as in patients with metabolic bone disorder. Results confirmed the North-South gradient of vitamin D levels described among European countries, despite the wide use of supplements. Although vitamin D supplementation is also recommended by the Italian Medicine Agency for patients at risk for fragility fracture or for initiating osteoporotic medication, the therapeutic gap for osteoporosis in Italy is very high. There is a consistent proportion of osteoporotic patients not receiving specific therapy for osteoporosis following a fragility fracture, with a poor adherence to the recommendations provided by national guidelines and position paper documents. The failure or inadequate supplementation with vitamin D in patients on antiresorptive or anabolic treatment for osteoporosis is thought to further amplify the problem and exposes patients to a high risk of re-fracture and mortality. Therefore, it is important that attention to its possible clinical consequences must be given. Thus, in light of new evidence from the literature, the SIOMMMS board felt the need to revise and update, by a GRADE/PICO system approach, its previous original recommendations about the definition, prevention, and treatment of vitamin D deficiency in adults, released in 2011. Several key points have been here addressed, such as the definition of the vitamin D status: normality values and optimal values; who are the subjects considered at risk of hypovitaminosis D; opportunity or not of performing the biochemical assessment of serum 25(OH)D levels in general population and in subjects at risk of hypovitaminosis D; the need or not to evaluate baseline serum 25(OH)D in candidate subjects for pharmacological treatment for osteoporosis; how and whether to supplement vitamin D subjects with hypovitaminosis D or candidates for pharmacological treatment with bone active agents, and the general population; how and whether to supplement vitamin D in chronic kidney disease and/or chronic liver diseases or under treatment with drugs interfering with hepatic metabolism; and finally, if vitamin D may have toxic effects in the subject in need of supplementation.

This narrative report summarizes diagnostic criteria for hypoparathyroidism and describes the clinical presentation and underlying genetic causes of the nonsurgical forms. We conducted a comprehensive literature search from January 2000 to January 2021 and included landmark articles before 2000, presenting a comprehensive update of these topics and suggesting a research agenda to improve diagnosis and, eventually, the prognosis of the disease. Hypoparathyroidism, which is characterized by insufficient secretion of parathyroid hormone (PTH) leading to hypocalcemia, is diagnosed on biochemical grounds. Low albumin-adjusted calcium or ionized calcium with concurrent inappropriately low serum PTH concentration are the hallmarks of the disease. In this review, we discuss the characteristics and pitfalls in measuring calcium and PTH. We also undertook a systematic review addressing the utility of measuring calcium and PTH within 24 hours after total thyroidectomy to predict long-term hypoparathyroidism. A summary of the findings is presented here; results of the detailed systematic review are published separately in this issue of JBMR. Several genetic disorders can present with hypoparathyroidism, either as an isolated disease or as part of a syndrome. A positive family history and, in the case of complex diseases, characteristic comorbidities raise the clinical suspicion of a genetic disorder. In addition to these disorders' phenotypic characteristics, which include autoimmune diseases, we discuss approaches for the genetic diagnosis. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

The COVID-19 pandemic and its consequences have demonstrated that viral infections still pose great challenge to health systems worldwide. The immune system plays a primary role in fighting infections, and non-specific innate immunity, in particular, is a key defense mechanism engaged during the first phases of an infection. The subsequent triggered immune response, characterized by specific cytokine patterns, can be exaggerated and lead to a cytokine storm, causing multiorgan damage and intravascular disseminated coagulation. Calcitriol, the active form of vitamin D, a key player in mineral homeostasis, is able to control the immune response by favoring the production of antimicrobial peptides (e.g., cathelicidin), decreasing viral shedding, and modulating the inflammatory process. A poor vitamin D status has been demonstrated to be associated with increased risk of infections, especially in fragile subjects, as also recently shown in COVID-19 disease. Unfortunately, this does not demonstrate that supplementation with vitamin D is significantly linked to prevention or modulation of the course of viral infections. Large intervention trials are necessary to produce evidence that vitamin D supplementation is linked to decreased rates of infections and related complications. At present, cholecalciferol and calcidiol regimens commonly employed in clinical practice to prevent and correct musculoskeletal abnormalities are advisable, at least in fragile, vitamin D-deficient individuals, in order to reach a target of serum 25(OH)D of 30–50 ng/ml, avoiding large doses, which can be responsible for hypercalciuria-hypercalcemia or increased falls.

Pregnancy is a delicate phase in woman's life that could become a risk factor for osteoporosis in pregnant women who do not meet recommended nutrient standards, especially for calcium and vitamin D. Mediterranean diet (MD) has been demonstrated to be beneficial for adequate nutrient intake. This article aims to evaluate the MD adherence and dietary calcium intake in a group of pregnant Italian women and to investigate how these are linked to each other and to fast glycemia at first trimester of pregnancy. Two hundred and seventy‐nine pregnant women were recruited at the gynecology units of two hospitals in Florence. Socio‐demographic, clinical information, and results of the first trimester blood sample analysis were collected. Two questionnaires, validated for evaluation of MD adherence and calcium intake, were administered to the pregnant women. Approximately 60% of the women had a high level of MD adherence, with a mean dietary calcium intake of 870.3 ± 335.3. In women with higher MD adherence level, fast glycemia resulted lower. Calcium intake was lower than Population Rate Intake for the Italian population (1,200 mg/daily) and was positively correlated to MD adherence score. The MD proved to be nutritious, as it was related to a higher calcium intake in this group of Italian women., MD adherence was positively correlated with higher calcium intake and lower fast glycemia at first trimester of pregnancy, in this population of 279 Italian pregnant women. The administration of validated questionnaires to evaluate MD adherence and calcium intake during pregnancy, through a short‐time interview (15‐20 minutes), could be inserted as a procedure of the Good Clinical Practice to prevent OP and GDM in pregnant women and to promote correct skeletal development in fetus.

Purpose: To update knowledge on dietary calcium intake in the Italian population, focusing on subjects of any age over 18 years. Methods: Data were collected through consecutive surveys, carried out from 2013 to 2018 in several Italian cities, during screening events intended to promote bone health among the Italian population. A Food Frequency Questionnaire (FFQ), validated for the assessment of the intake of calcium and nutrients for bone health in adults, was administered to subjects to estimate calcium intake in all groups. Results: Out of a total of 1821 FFQs filled in, 1801 provided all the information necessary for the evaluation of calcium intake (being correctly completed and indicating gender and age). Median values were significantly lower than the Italian population reference intake (PRI) values in women of all ages (range: 792 to 854.1 mg/day) and in men aged 60-74 years (854 mg/day) and over 75 years (832.1 mg/day). Young adult males (18-29 years) and adult males (30-59 years) consumed calcium in quantities close to the recommended amounts. Conclusions: These results are in line with what has already been observed in subsets of the Italian population. For this reason, it is once again appropriate to reiterate the need to plan suitable campaigns to spread information and provide guidelines on adequate nutrition able to guarantee correct calcium intake.

Both osteoporosis with related fragility fractures and cardiovascular diseases are rapidly outspreading worldwide. Since they are often coexistent in elderly patients and may be related to possible common pathogenetic mechanisms, the possible reciprocal effects of drugs employed to treat these diseases have to be considered in clinical practice. Bisphosphonates, the agents most largely employed to decrease bone fragility, have been shown to be overall safe with respect to cardiovascular diseases and even capable of reducing cardiovascular morbidity in some settings, as mainly shown by real life studies. No randomized controlled trials with cardiovascular outcomes as primary endpoints are available. While contradictory results have emerged about a possible BSP-mediated reduction of overall mortality, it is undeniable that these drugs can be employed safely in patients with high fracture risk, since no increased mortality has ever been demonstrated. Although partial reassurance has emerged from meta-analysis assessing the risk of cardiac arrhythmias during bisphosphonates treatment, caution is warranted in administering this class of drugs to patients at risk for atrial fibrillation, possibly preferring other antiresorptives or anabolics, according to osteoporosis guidelines. This paper focuses on the complex relationship between bisphosphonates use and cardiovascular disease and possible co-management issues.

Abstract. 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.

Purpose Tumor induced osteomalacia (TIO) is a rare disease of mineral metabolism, whose clinical picture is dominated by hypophosphatemia usually due to an excess of circulating FGF23 produced by small mesenchymal tumors. Data on the real prevalence of the disease are lacking, with the knowledge of the disease mainly relying on case reports and small case series. No estimate is available on the prevalence of uncured TIO. Methods National multi-center, cross-sectional and retrospective study on persistent or recurrent cases of TIO followed in referral centers for bone diseases; systematic review of the published persistent and recurrent cases of TIO. Data from patients consecutively evaluated in referral Italian centers for bone diseases were collected; a PubMed search on persistent, recurrent and unoperable cases of TIO was carried out. Results Sixteen patients (mean age at diagnosis 52.5 ± 10.6 years) with persistent (n = 6, 37,5%), recurrent (n = 7, 43.7%) or not operable (n = 3, 18.8%) TIO were described. Delay in diagnosis (2.5 ± 1.3 years) was demonstrated. All patients experienced fragility fractures or pseudofractures and disabling bone and muscle pain. BMD was significantly reduced (mean T-score −2.7 ± 1.7 and −2.7 ± 0.9 at lumbar spine and femoral neck, respectively). Fourteen patients were maintained under therapy with phosphate salts and calcitriol, while in 2 patients therapy with burosumab, an anti-FGF23 antibody, was commenced. Conclusion A significant number of patients with TIO remain either undiagnosed for tumor localization or tumor recur or persist after surgery. These patients with active disease represent possible candidates for burosumab treatment.

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.

Vascular calcification and fragility fractures are associated with high morbidity and mortality, especially in end-stage renal disease. We evaluated the relationship of iliac arteries calcifications (IACs) and abdominal aortic calcifications (AACs) with the risk for vertebral fractures (VFs) in hemodialysis patients. The VIKI study was a multicenter cross-sectional study involving 387 hemodialysis patients. The biochemical data included bone health markers, such as vitamin K levels, vitamin K-dependent proteins, vitamin 25(OH)D, alkaline phosphatase, parathormone, calcium, and phosphate. VF, IACs and AACs was determined through standardized spine radiograms. VF was defined as &gt, 20% reduction of vertebral body height, and VC were quantified by measuring the length of calcium deposits along the arteries. The prevalence of IACs and AACs were 56.1% and 80.6%, respectively. After adjusting for confounding variables, the presence of IACs was associated with 73% higher odds of VF (p = 0.028), whereas we found no association (p = 0.294) for AACs. IACs were associated with VF irrespective of calcification severity. Patients with IACs had lower levels of vitamin K2 and menaquinone 7 (0.99 vs. 1.15 ng/mL, p = 0.003), and this deficiency became greater with adjustment for triglycerides (0.57 vs. 0.87 ng/mL, p &lt, 0.001). IACs, regardless of their extent, are a clinically relevant risk factor for VFs. The association is enhanced by adjusting for vitamin K, a main player in bone and vascular health. To our knowledge these results are the first in the literature. Prospective studies are needed to confirm these findings both in chronic kidney disease and in the general population.

Context Hypophosphatasia (HPP) is a rare metabolic disorder caused by deficiency of alkaline phosphatase (ALP) enzyme activity, leading to defective mineralization, due to pathogenic variants of the ALPL gene, encoding the tissue nonspecific alkaline phosphatase (TNSALP) enzyme. Inheritance can be autosomal recessive or autosomal dominant. An abnormal ALPL genetic test enables accurate diagnosis, avoiding the administration of contraindicated antiresorptive drugs that, in patients with HPP, substantially increase the risk of atypical femur fractures (AFFs) and worsen the fracture healing process that is usually already compromised in these patients. Objective Performing ALPL genetic testing to identify rare variants in suspected adult patients with HPP. Comparing frequencies of ALPL common variants in individuals with biochemical and/or clinical signs suggestive of adult HPP and non-HPP controls, and among different clinical subgroups of patients with a clinical suspicion of adult HPP. Methods Patients with suspected adult HPP were retrospectively selected for the genetic testing of the ALPL gene. Patients included were from 3 main European Bone Units (Florence, Naples, and Geneva); 106 patients with biochemical and/or clinical signs suggestive of a mild form of HPP were included. Results Genetic testing led to the identification of a heterozygote rare variant in 2.8% of cases who were initially referred as suspected osteoporosis. The analysis of frequencies of ALPL common variants showed a high prevalence (30.8%) of homozygosity in subjects who developed an AFF, in association with normal serum total ALP activity. Conclusion The results suggest homozygosity of common ALPL variants as a possible genetic mark of risk for these fractures.

The parathyroid glands play a pivotal role in orchestrating mineral metabolism and maintaining serum calcium and phosphate levels within a narrow range. These ions themselves, together with other hormones classically implicated in their fine tuning, are able to regulate parathyroid function, establishing feedback mechanisms, which modulate parathyroid hormone (PTH) secretion. Calcium ions activate the calcium sensing receptor (CaSR) expressed on the parathyroid cell, triggering intracellular signaling able to inhibit PTH secretion. In conditions of hypocalcemia, these pathways are turned off and PTH is promptly released from the parathyroids. Recent findings have demonstrated that PTH secretion is a mechanism dependent on endonuclease Dicer and miRNA maturation. Although a specific phosphate sensor has yet to be identified, phosphate is also sensed by the parathyroids cells. High extracellular phosphate levels increase serum PTH levels, stabilizing PTH mRNA. Signals eliciting PTH synthesis and secretion are also able to induce parathyroid hyperplasia in the long term, inducing cell proliferation. A parathyroid cell culture model is needed to better dissect the mechanisms controlling PTH transcription and secretion and to test new compounds able to modulate the different intracellular signaling pathways.

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.

Summary We analyzed polymorphism of the ALPL gene in patients with low serum levels of tissue-nonspecific alkaline phosphatase (TNAP). The presence of three or more of the less frequent alleles of ALPL polymorphisms was associated with significantly lower TNAP serum level and higher frequencies of metatarsal fractures, which may help confirm a clinical suspicion of adult hypophosphatasia. Introduction Alkaline phosphatases (ALPs) are membrane-bound enzymes that hydrolyze monophosphate esters at a high pH (pH 8–10). Inorganic pyrophosphate, pyridoxal 5-phosphate, the activated form of vitamin B6 (PLP), and phosphoethanolamine (PEA), are natural substrates of ALPs. Hypophosphatasia (HPP, OMIM 146300, 241500, 241510) is a heterogeneous rare metabolic bone disease caused by loss-of-function mutations in the tissue-nonspecific alkaline phosphatase gene (ALPL; MIM 171760) with a deficiency of TNAP. Clinical presentation of HPP in adults demonstrated a wide range of manifestations, many of which are nonspecific. In the present study, we screened the polymorphic genetic variants of ALPL in 56 subjects presenting low serum levels of TNAP and/or other clinical signs of adult HPP in order to evaluate a possible role of polymorphic variants in the diagnosis and management of HPP in adults. Methods Genomic DNA was extracted from peripheral blood and ALPL gene was sequenced by PCR-based Sanger technique. Results Fourteen different polymorphic variants were found in the study population. A lower serum level of TNAP and higher frequencies of metatarsal fractures were observed in patients bearing three or more of the minor frequency alleles (MFAs) of the ALPL polymorphic variants. The presence of some MFAs, mostly as a contemporary presence of three or more of them, was found to be mainly represented in patients having both a significantly lower level of TNAP and a higher level of vitamin B6. Conclusion The genetic analysis and presence of some polymorphic variants may be an instrument to confirm clinical and biochemical data, consider adult HPP, and help clinicians be cautious in the administration of anti-reabsorption drugs.

The clinical manifestations of hypoparathyroidism are variable and can involve almost any organ system. The main clinical features of the hypoparathyroidism are typically signs or symptoms due to neuromuscular irritability owing to low serum calcium level. In addition to hypocalcemia, hyperphosphatemia can contribute to long-term complications, including extra-skeletal calcifications. Bone turnover markers are generally decreased, and bone mass density is usually normal-increased compared to age- and gender-matched controls. It is still unclear whether or not these bone features could have an impact on the risk of fracture. Impaired renal function is a common complication described in patients treated for hypoparathyroidism. Other complications include premature cataracts, seizures, basal ganglia calcifications, and cardiac arrhythmias. Lastly, some clinical studies have also reported a reduced quality of life of patients with hypoparathyroidism. Increased awareness of the clinical manifestations of this disease is important to improve its clinical management.

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. 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. 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. 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.

To investigate the effectiveness of the T-score values provided by Radiofrequency Echographic Multi Spectrometry (REMS) in the identification of patients at risk for incident osteoporotic fractures.A population of Caucasian women (30-90 years), enrolled from 2013 to 2016, underwent dual X-ray absorptiometry (DXA) and REMS scans at axial sites. The incidence of fragility fractures was assessed during a follow-up period up to 5 years. Afterwards, patients with and without incident fractures were stratified in two age-matched groups with a 1: 2 proportion (Group F' and Group NF', respectively). The performance of REMS T-score in discriminating between the two groups was quantitatively assessed and compared with DXA.1516 patients were enrolled and 1370 completed the follow-up (mean ± SD: 3.7 ± 0.8 years; range: 1.9-5.0 years). Fracture incidence was 14.0%. Age-matched groups included 175 fractured patients and 350 non-fractured ones, respectively (median age 70.2 [interquartile range: 61.0-73.3] and 67.3 [65.4-69.8] years, p-value ns). The groups resulted also balanced for height, weight and BMI (p-values ns). As expected, the differences in REMS T-score (for vertebral site, -2.9 [-3.6 to -1.9] in Group F', -2.2 [-2.9 to -1.2] in Group NF') and DXA T-score (-2.8 [-3.3 to -1.9] in Group F', -2.2 [-2.9 to -1.4] in Group NF') were statistically significant (p-value0.001). Analogous results were obtained for femoral neck. Considering the T-score cut-off of -2.5, REMS identified Group F' patients with a sensitivity of 65.1% and specificity of 57.7% of (OR = 2.6, 95%CI: 1.77-3.76, p 0.001), whereas DXA showed a sensitivity of 57.1% and a specificity of 56.3% (OR = 1.7, 95%CI: 1.20-2.51, p-value = 0.0032). For femoral neck, REMS sensitivity and specificity were 40.2% and 79.9%, respectively, with an OR of 2.81 (95%CI: 1.80-4.39, p 0.001). DXA, instead, showed a sensitivity and specificity of 42.3% and 79.3%, respectively, with an OR of 2.68 (95%CI: 1.71-4.21, p 0.001).REMS T-score resulted an effective predictor for the risk of incident fragility fractures in a population-based sample of female subjects, representing a promising parameter to enhance osteoporosis diagnosis in the clinical routine.

Background To date numerous quantitative methods to diagnose osteoporosis at peripheral sites have been developed. REMS (Radiofrequency Echographic Multi Spectrometry) is a non-ionizing instrument used to quantitatively evaluate bone mineral density at lumbar spine and femoral neck sites [1]. Objectives To assess the accuracy of REMS in osteoporosis diagnosis at axial sites (lumbar spine and hip) compared with the gold standard, Dual-energy X-ray absorptiometry (DXA). Methods We enrolled patients aged from 50 to 75 years and perfomed a total of 1,699 and 1,794 lumbar spine and proximal femur scans with REMS and DXA. A quality checks on DXA and REMS acquired data were performed through direct examination of scans by experienced operators. We investigated the agreement between the two techniques calculating: Pearson`s correlation coefficient (r), Standard Error of the Estimate (SEE) and efficiency (sensitivity and specificity) in identifying osteoporotic individuals (i.e. T-score ≤ -2.5). Results We found a good linear correlation between REMS and DXA BMD estimation, Pearson coefficient r=0.938 for lumbar spine and r=0.933 for proximal femur (p Conclusion REMS exhibited a high sensitivity and specificity in identifying osteoporotic patients at lumbar spine or proximal femur sites compared with gold-standard DXA. REMS accurately diagnosed osteoporotic patients in clinical routine, at both lumbar spine and proximal femur sites, without using ionizing radiation. References [1] Di Paola M, Gatti D, Viapiana O, et al. Osteoporos Int, 2018 Disclosure of Interests Giovanni Adami: None declared, Giovanni Arioli: None declared, Gerolamo Bianchi: None declared, Maria Luisa Brandi: None declared, Carla Caffarelli: None declared, Loredana Cavalli: None declared, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Pfizer, BMS, Chemomab, Sanipedia, Speakers bureau: Actelion, BMS; MSD, Janssen, Luisella Cianferotti Speakers bureau: Abiogen Pharma, Bruno Farmaceutici, Shire, Francesco Conversano Shareholder of: Francesco Conversano own stocks of Echolight Spa, Marco Di Paola: None declared, Davide Gatti Speakers bureau: Abiogen, Amgen, Janssen-Cilag, Mundipharma, Pfeizer, Giuseppe Girasole: None declared, Andrea Giusti: None declared, Stefano Gonnelli: None declared, Monica Manfedini: None declared, Maurizio Muratore: None declared, Ranuccio Nuti: None declared, Paola Pisani: None declared, Laura Quarta: None declared, Ombretta Viapiana Speakers bureau: Novartis, Abbvie, Eli-Lilly, Sanofi Genzyme

Background Scientific interest in the clinical aspects surrounding vitamin D has increased exponentially in recent years. Unfortunately, this interest is not currently associated with a proportional level of consensus. Indeed, the large number of studies in this field, which are often of low quality and secondary importance has confused even experts and driven them towards controversial positions. Objectives To shed light on this topic, we arranged a meeting with the aim of collecting the opinions of 50 experts in different specialties (“D..Battito Group”), including internists, endocrinologists, rheumatologists, pediatricians, geriatricians, dermatologists, gynecologists and nephrologists. This meeting dealt with specific questions regarding the management of hypovitaminosis D and aimed to investigate the opinions of Italian experts on this topic. Six key questions were addressed in the meeting. Methods After a short lecture and a 30 minutes discussion, all the experts expressed their opinions, which were recorded together with any specific commentary. Results The results of the meeting demonstrated the presence of insufficient agreement on many key questions regarding the management of vitamin D deficiency, even among clinical experts. Conclusion We hope that the various scientific societies will recognize and analyze the inconsistencies in their own positions and reach adequate consensus, especially on the tenets required for conducting proper and useful investigations on the topic, and that the results of these future new studies will be able to shed the needed light. Acknowledgement Abdel Jaber M, Benini C, Boner A, Bortolotti R, Brigo M, Catalano A, Ferlin A, Girasole G, Idolazzi L, Lello S, Maestri E, Martinis F, Muratore M, Olivari F, Peroni D, Romagnoli E, Ruggiero C, Saviola G, Sella S, Sfrappini M, Silveri F, Vantaggiato E, Venturin A, Zuccaro C. Disclosure of Interests Alessandro Giollo: None declared, Ombretta Viapiana Speakers bureau: Novartis, Abbvie, Eli-Lilly, Sanofi Genzyme, Angelo Fassio Speakers bureau: Abiogen Pharma, Francesco Bertoldo: None declared, Vania Teresa Braga: None declared, Maria Luisa Brandi: None declared, Stefano Calvieri: None declared, Luisella Cianferotti Speakers bureau: Abiogen Pharma, Bruno Farmaceutici, Shire, Annamaria Colao: None declared, Patrizia D’Amelio: None declared, Giovanni Mario D’Avola: None declared, Luca Degli Esposti: None declared, Bruno Frediani: None declared, Sandro Giannini: None declared, Andrea Giusti Grant/research support from: Abiogen Pharma, Consultant for: EffRx, Speakers bureau: Abiogen Pharma, Eli Lilly, AMGEN, Andrea Giustina: None declared, Stefano Gonnelli: None declared, Nazzarena Malavolta: None declared, Claudio Marcocci Grant/research support from: Shire, Speakers bureau: Shire and AbiogenPharma, Salvatore Minisola: None declared, Nicola Napoli: None declared, Ranuccio Nuti: None declared, Giovanni Passeri Grant/research support from: Abiogen Pharma and Chiesi Farmaceutici, Speakers bureau: Abiogen Pharma and Chiesi Farmaceutici, Maurizio Rossini: None declared, Luigi Sinigaglia: None declared, Francesco Vierucci: None declared, Davide Gatti Speakers bureau: Abiogen, Amgen, Janssen-Cilag, Mundipharma, Pfeizer

The endocrine system is frequently altered after a major burn trauma. Besides the endocrine response to stress characterized by hypercortisolism, several hypothalamus-hypophysis-target gland axes are rapidly perturbed within a few days. These alterations can persist in the long term and deserve an appropriate treatment. Disturbances in water clearance and glucidic metabolism are also common and need to be diagnosed and corrected to decrease morbidity in such patients. Bone and mineral metabolism is deeply compromised and requires correction of mineral abnormalities in order to improve symptoms and prevent bone loss. No large prospective and/or intervention trials are available to date to elaborate age-related, evidence-based recommendations to monitor and treat burn-related endocrine alterations.

“Nudge” policies are increasingly popular, seeking to modify health-related decisions by affecting response to available options. Thus, critical appraisals of the effectiveness of health-related nudging interventions could help health policy makers in making evidence-based decisions with regards to which of these interventions should be incorporated into policy. The aim of the present effort was to systematically appraise the evidence on nudging interventions on healthy diet and physical activity (PA). A systematic review was performed using Pubmed, Web of Science Core Collection citation index and the Cochrane Controlled Register of Trials (CENTRAL). Interventional studies were included if they quantitatively assessed healthy diet and/or PA interventions that were explicitly related to a nudging context. Methodological assessment was performed using the Cochrane collaboration’s risk of bias tool and the Research Triangle Institute item bank. Sixty-four studies were included with varying degrees of bias. Sixty studies investigated healthy diet interventions, three studied PA interventions and one studied interventions pertaining to both. Overall, specific types of interventions such as proximity and presentation alterations can be effective in encouraging people towards the adoption of healthier diet choices, whereas labelling, availability, prompting, functional design and sizing “nudge” interventions provide inconclusive results so far. Nudging interventions improving convenience seem to be effective in encouraging people towards making healthier diet choices, whereas evidence on PA is limited. Further conceptual development and research is needed to optimally determine the type, intensity and circumstances that make nudge-related interventions more effective, particularly regarding PA.

This study investigates the relationship between cognitive dysfunction or delirium detected in the early post-surgical phase and the 1-year mortality among 514 hip fracture hospitalized older persons. Patients with early cognitive dysfunction or delirium experienced a 2-fold increased mortality risk. Early post-operative cognitive dysfunction and delirium are negative prognostic factors for mortality. Premorbid cognitive impairment and dementia in older individuals negatively affect functional recovery after hip fracture. Additionally, post-operative delirium is an established risk factor for negative outcomes among hip fracture patients. While the majority of hip fracture patients experience minor post-surgical cognitive dysfunction, the prognostic value of this phenomenon is unknown. Therefore, we investigated the relationship between minor cognitive dysfunction or delirium detected in the early post-surgical phase and the 1-year mortality after index hip fracture. We enrolled 514 patients with hip fracture (77.4 % women), aged 65 years or older (mean age 83.1 ± 7.3 years), who underwent surgical hip fracture repair. Patients were assessed daily from the second to the fourth post-operative day and at 3, 6, and 12 months thereafter. All participants underwent comprehensive assessment, including detection of delirium by using the confusion assessment method and evaluation of cognitive function by using mini-mental state examination (MMSE; score range 0 to 30, with lower scores indicating poorer performance). In the absence of delirium, post-surgical cognitive dysfunction was defined as having low performance on MMSE. Vital status of 1 year after the index fracture and date of death were gathered from local registries. The observed 1-year mortality rate was 14.8 %. Men were more likely to die than women within 1 year of the index fracture (p

Background:The monitoring of bone mineral density (BMD) is a key aspect for patients undergoing pharmacological treatments that might cause BMD changes at non-physiological rates. At present, the short-term follow-up of patients under treatment in terms of BMD change with time remains an unmet clinical need, since the current techniques, including the gold standard dual X-ray absorptiometry (DXA), require at least 1 year between two consecutive measurements [1]. Therefore, an effective strategy for the assessment of BMD should guarantee high accuracy, precision and repeatability of the measurements.Objectives:The aim is to assess the influence of the variation 1) in patient position, 2) operator (both intra- and inter-) and 3) device on the REMS performance at lumbar spine and femoral neck.Methods:210 women were enrolled, divided in 7 groups of 30-patient each for the assessment of the parameters of interest, i.e. inter-device, intra- and inter-operator repeatability for lumbar spine scans and inter-patient position, inter-device, intra- and inter-operator repeatability for femoral neck scans.All patients underwent 2 REMS scans at lumbar spine or femoral neck, performed by the same operator or by 2 different operators or by the same operator using 2 different devices or in different patient position (i.e. supine without constraints or with a constrained 25°-rotation of the leg). The percentage coefficient of variation (CV%) with 95% confidence interval and least significant change for a 95% confidence level (LSC) have been calculated.Results:For lumbar spine, intra-operator repeatability resulted in CV%=0.37% (95%CI: 0.26%-0.48%), with LSC=1.02%, inter-operator repeatability resulted in CV%=0.55% (95% CI: 0.42%-0.68%), with LSC=1.52%, inter-device repeatability resulted in CV%=0.53% (95% CI: 0.40%-0.66%), with LSC=1.47%.For femoral neck, intra-operator repeatability resulted in CV%=0.33% (95%CI: 0.23%-0.43%), with LSC=0.91%, inter-operator repeatability resulted in CV%=0.47% (95% CI: 0.35%-0.59%), with LSC=1.30%, inter-device repeatability resulted in CV%=0.42% (95% CI: 0.30%-0.51%), with LSC=1.16%, inter-patient position repeatability resulted in CV%=0.24% (95% CI: 0.18%-0.30%), with LSC=0.66%.Conclusion:REMS densitometry is highly precise for both anatomical sites, showing high performance in repeatability. These results suggest that REMS might be a suitable technology for short-term monitoring. Moreover, thanks to its ionizing radiation-free approach, it might be applied for population mass investigations and prevention programs also in paediatric patients and pregnant women.References:Note:Carla Caffarelli, Giovanni Adami§, Giovanni Arioli§, Gerolamo Bianchi§, Maria Luisa Brandi§, Sergio Casciaro§, Luisella Cianferotti§, Delia Ciardo§, Francesco Conversano§, Davide Gatti§, Giuseppe Girasole§, Monica Manfredini§, Maurizio Muratore§, Paola Pisani§, Eugenio Quarta§, Laura Quarta§, Stefano Gonnelli§Equal contributors listed in alphabetical orderDisclosure of Interests:Carla Caffarelli: None declared, Giovanni Adami: None declared, Giovanni Arioli *: None declared, Gerolamo Bianchi Grant/research support from: Celgene, Consultant of: Amgen, Janssen, Merck Sharp & Dohme, Novartis, UCB, Speakers bureau: Abbvie, Abiogen, Alfa-Sigma, Amgen, BMS, Celgene, Chiesi, Eli Lilly, GSK, Janssen, Medac, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sanofi Genzyme, Servier, UCB, Maria Luisa Brandi: None declared, Sergio Casciaro: None declared, Luisella Cianferotti: None declared, Delia Ciardo: None declared, Francesco Conversano: None declared, Davide Gatti Speakers bureau: Davide Gatti reports personal fees from Abiogen, Amgen, Janssen-Cilag, Mundipharma, outside the submitted work., Giuseppe Girasole: None declared, Monica Manfedini: None declared, Maurizio Muratore: None declared, Paola Pisani: None declared, Eugenio Quarta: None declared, Laura Quarta: None declared, Stefano Gonnelli: None declared

Background:Radiofrequency Echographic Multi Spectrometry (REMS) is the first clinically available approach for direct non-ionizing measurement of bone mineral density (BMD) at lumbar spine (LS) and femoral neck (FN). Available scientific evidences describe BMD estimated by REMS as an accurate parameter for the diagnosis of osteoporosis [1].Objectives:To investigate the effectiveness of the T-score values provided by REMS scans at FN and LS in the identification of frail patients at risk for osteoporotic fractures and to compare the performance of REMS with the dual-energy X-ray absorptiometry (DXA) one.Methods:The patients underwent DXA and REMS scans at FN and at LS. Five clusters of fractures occurred during a median 3.5-year follow-up were identified whether involving the upper limb (forearm, elbow, humerus, wrist, hand), lower limb (tibia, ankle, metatarsus), thorax (shoulder blade, shoulder, rib), hip (femur or pelvis bones), or vertebrae. The ability of REMS and DXA T-score values to assess the incidence and site of fractures was evaluated through an analysis of covariance.Results:Seven hundred twenty-one Caucasian women were enrolled. Ninety-five fractures occurred, in particular 41 at upper limb, 16 at hip, 15 at thorax, 14 at lower limb, 9 at vertebrae. Patients characteristics are reported in table. Considering subcategories of fractured patients, there were not statistically significant differences for age, height, weight and BMI.In the analysis of covariance including age and BMI as covariates, the difference of T-score values between fractured and non-fractured patients is statistically significant for REMS and DXA at both sites.Lower FN T-score values were found for patients with fractures at hip or vertebra with respect to non-fractured patients both for REMS and DXA (pConclusion:REMS T-score measured at axial sites is an effective parameter for identification of patients at the risk of incident fragility fractures, in particular occurring at hip, vertebra or upper limb in a population-based sample of female subjects.References:[1]Diez-Perez, Aging Clin Exp Res 2019;31(10):1375–89Table 1.Baseline patient characteristics, expressed as median (25th– 75thpercentiles).Patients with incident fragility fracturePatients without incident fragility fracturep-value*Age [years]70 (60-73)59 (54-64)Height [cm]159 (155-164)160 (156-165)0.08Weight [kg]63 (58-70)62 (57-69)0.42BMI [kg/m2]24.97 (23.13-26.86)24.24 (22.22-26.59)0.04FN REMS T-score-2.3 (-2.8 – -1.7)-1.8 (-2.3 – -1.1)FN DXA T-score-2.2 (-2.8 – -1.6)-1.7 (-2.3 – -1.1)LS REMS T-score-3.0 (-3.5 – -2.0)-2.0 (-2.8 – -1.0)LS DXA T-score-2.8 (-3.4 – -1.8)-1.9 (-2.7 – -1.0)* Wilcoxon ranksum testFigure.Boxplot of the distribution of T-score values estimated REMS and DXA at FN and LS among patients without incident fragility fracture and patients with incident fragility fractures at different sites.Note:G. Adami, G. Arioli§, G. Bianchi§, M.L. Brandi§, C. Caffarelli§, L. Cianferotti§, G. Girasole§, S. Gonnelli§, M. Manfredini§, M. Muratore§, E. Quarta§, L. Quarta§, D. Gatti§ equal contributors listed in alphabetical order.Disclosure of Interests:Giovanni Adami: None declared, Giovanni Arioli *: None declared, Gerolamo Bianchi Grant/research support from: Celgene, Consultant of: Amgen, Janssen, Merck Sharp & Dohme, Novartis, UCB, Speakers bureau: Abbvie, Abiogen, Alfa-Sigma, Amgen, BMS, Celgene, Chiesi, Eli Lilly, GSK, Janssen, Medac, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sanofi Genzyme, Servier, UCB, Maria Luisa Brandi: None declared, Carla Caffarelli: None declared, Luisella Cianferotti: None declared, Giuseppe Girasole: None declared, Stefano Gonnelli: None declared, Monica Manfedini: None declared, Maurizio Muratore: None declared, Eugenio Quarta: None declared, Laura Quarta: None declared, Davide Gatti Speakers bureau: Davide Gatti reports personal fees from Abiogen, Amgen, Janssen-Cilag, Mundipharma, outside the submitted work.

Hypoparathyroidism, a disorder characterized by hypocalcemia ensuing from inadequate parathyroid hormone secretion, is a rather rare disorder caused by multiple etiologies. When not caused by inadvertent damage or removal of the parathyroids during neck surgery, it is usually genetically determined. Epidemiological figures of this disease are still scarce and mainly limited to countries where non-anonymous databases are available and to surgical case series. Both the surgical and non-surgical forms pose diagnostic challenges. For surgical hypoparathyroidism, transient forms have to be ruled out even in the long term, in order to avoid unnecessary chronic replacement therapy with calcium and calcitriol. Regarding non-surgical hypoparathyroidism, once referred to as idiopathic, a systematic clinically and genetically-driven approach to define the precise diagnosis have to be pursued. In the case of syndromic hypoparathyroidism, patients have to be screened for associated abnormalities. Autoimmune, non-genetic hypoparathyroidism is still a diagnosis of exclusion, since no specific autoantibodies are specific for this condition.

The term hypoparathyroidism encompasses a huge group of disorders all characterized by an abnormal mineral homeostasis determined by inadequate secretion of parathyroid hormone. Postsurgical hypoparathyroidism is a complication of neck surgery (thyroidectomy, parathyroidectomy, lymph node, and cancer neck dissection), closely related to the extent of the surgical procedure and the experience of the surgeon. If lasting more than 6 months it is defined as chronic hypoparathyroidism, requiring life-long replacement therapy with active vitamin D metabolites. All the other forms of nonsurgical hypoparathyroidism, previously referred to as idiopathic hypoparathyroidism, have several causes, the majority of them genetic, which can be grouped into 3 main categories: disorder of parathyroid development, disorders of parathyroid function, and acquired damage to the parathyroids. Hypoparathyroidism can manifest as the sole disease in an individual (isolated hypoparathyroidism) or be associated with other manifestations within complex syndromes (syndromic hypoparathyroidism). Functional hypoparathyroidism, which may be caused by magnesium disturbances, has always to be ruled out before commencing the genetic diagnostic workup in nonsurgical forms. The search for signs of autoimmunity can drive the diagnosis towards an autoimmune pathogenesis of the disease, since a routine assessment of parathyroid autoantibodies is neither available nor specific.

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.

The term hypoparathyroidism encompasses a huge group of disorders all characterized by an abnormal mineral homeostasis determined by inadequate secretion of parathyroid hormone. Postsurgical hypoparathyroidism is a complication of neck surgery (thyroidectomy, parathyroidectomy, lymph node, and cancer neck dissection), closely related to the extent of the surgical procedure and the experience of the surgeon. If lasting more than 6 months it is defined as chronic hypoparathyroidism, requiring life-long replacement therapy with active vitamin D metabolites. All the other forms of nonsurgical hypoparathyroidism, previously referred to as idiopathic hypoparathyroidism, have several causes, the majority of them genetic, which can be grouped into 3 main categories: disorder of parathyroid development, disorders of parathyroid function, and acquired damage to the parathyroids. Hypoparathyroidism can manifest as the sole disease in an individual (isolated hypoparathyroidism) or be associated with other manifestations within complex syndromes (syndromic hypoparathyroidism). Functional hypoparathyroidism, which may be caused by magnesium disturbances, has always to be ruled out before commencing the genetic diagnostic workup in nonsurgical forms. The search for signs of autoimmunity can drive the diagnosis towards an autoimmune pathogenesis of the disease, since a routine assessment of parathyroid autoantibodies is neither available nor specific.

The original version of this article unfortunately contained a mistake in Table 2. The table 2 was truncated in the original publication. The full table 2 is given below.

Background Radiofrequency Echographic Multi Spectrometry (REMS) is an innovative densitometric technique able to automatically provide BMD values, which it has been shown to highly correlate with BMD obtained by DXA.1 Objectives To evaluate the accuracy of REMS measurements in postmenopausal women’s femoral neck health assessment versus DXA results in a multicenter clinical study. Methods In seven Italian referral centres for osteoporosis management, 1659 postmenopausal women (51–70 years old) were enrolled. Both DXA and REMS examinations were performed on each patient at femoral neck, in the strictest adherence to the corresponding guidelines. After excluding the scans affecting by errors, the REMS diagnostic accuracy was evaluated by assessing sensibility and specificity in the discrimination between “osteoporotic” and “healthy” patients; the degree of correlation between DXA-BMD and REMS-BMD was quantified through Pearson’s correlation coefficient (r) evaluation. In addition, the agreement between DXA-BMD and REMS-BMD was measured calculating the root mean square error (RMSE). Results A strong correlation (r=0.94, p Conclusions Thanks to its high capability to identify osteoporotic patients, and the strong correlation with DXA parameters, REMS has been shown to be an accurate non-ionising approach to detect osteoporosis at femoral neck. Reference [1] Casciaro S, et al. UMB2016;42:1337–56. Disclosure of Interest None declared

Optimal peak bone mass and bone health later in life are favored by a sufficient calcium intake in infancy, childhood and adolescence. The purpose of this study was to test a new educational program created to monitor and to improve calcium and vitamin D intake in children. Nutritional habits in children were evaluated through a food frequency questionnaire (FFQ) to assess the intake of calcium, vitamin D, dairy products, and total caloric energy at baseline and after seven months of exposure to a unique educational program applied between November 2013 and May 2014 in 176 schoolchildren (48% male, 52% female) attending the fourth and fifth grades of two selected primary schools in Florence, Italy. A significant increase of calcium (from 870 ± 190 to 1100 ± 200 mg/day, p &lt, 0.05), and vitamin D (from 3.6 ± 1.53 to 4.1 ± 2 µg/day) intake in children was documented after the educational program. The amount of specific foods important for bone health consumed, such as milk and vegetables, increased significantly, both in male and female children (p &lt, 0.05). The proposed educational program appears to be effective in modifying calcium intake in children, with a significant increase in the consumption of dairy products and vegetables, but without a significant change in the total caloric intake.

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.

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.

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.

Objectives The randomized controlled trial examined factors that might be responsible for individual differences in physical activity change among men and women who participated in a lifestyle intervention. The main purpose of the analyses regarded the role of psychological mechanisms involving motivation, planning, self-monitoring, and habit strength. Design A two-arm digital intervention was conducted in Italy, Spain, and Greece to improve physical activity levels, with follow-ups at 3 and 6 months after baseline assessment. Methods Participants were 1,564 adults at baseline, n = 638 at 6-month follow-up. Linear mixed models examined the intervention effects, and a two-group longitudinal structural equation model explored which psychological constructs (motivation, planning, self-monitoring, habit strength) were associated with changes in physical activity. Results In addition to an overall increase in self-reported activity, there were interactions between time and sex and between time and experimental groups, and a triple interaction between time, sex, and experimental groups, indicating that men reported an increase in activity independent of groups, whereas women in the active control group did not benefit from the intervention. Planning, self-monitoring, and habit strength mediated sequentially between initial motivation and follow-up physical activity. Conclusions Although the intervention produced overall improvements in physical activity, the time-by-treatment interaction emerged only for women. The mechanism included a sequence leading from motivation via planning, self-monitoring, and habit strength towards physical activity. Statement of contribution What is already known on this subject? Digital lifestyle interventions can be effective in terms of physical activity performance gains. Men are on average more physically active than women. Long-term adherence rates to digital interventions are usually low. What does this study add? Giving users of an online platform more interactive options did not make a difference. Women gained more than men from adaptive, dynamic online platform content. Individual characteristics (motivation, planning, self-monitoring, habit) were more important than online treatment features.

Purpose: Evaluation of the phenotype of primary hyperparathyroidism (PHPT), adherence to International Guidelines for parathyroidectomy (PTx), and rate of surgical cure. Method: From January 2014–January 2016, we performed a prospective, multicenter study in patients with newly diagnosed PHPT. Biochemical and instrumental data were collected at baseline and during 1-year follow-up. Results: Over the first year we enrolled 604 patients (age 61 ± 14years), mostly women (83%), referred for further evaluation and treatment advice. Five hundred sixty-six patients had sporadic PHPT (93.7%, age 63 ± 13 years), the remaining 38 (6.3%, age 41 ± 17 years) had familial PHPT. The majority of patients (59%) were asymptomatic. Surgery was advised in 281 (46.5%). Follow-up data were available in 345 patients. Eighty-seven of 158 (55.1%) symptomatic patients underwent PTx. Sixty-five (53.7%) of 121 asymptomatic patients with at least one criterion for surgery underwent PTx and 56 (46.3%) were followed without surgery. Negative parathyroid imaging studies predicted a conservative approach [symptomatic PHPT: OR 18.0 (95% CI 4.2–81.0) P < 0.001; asymptomatic PHPT: OR 10.8, (95% CI 3.1–37.15) P < 0.001). PTx was also performed in 16 of 66 (25.7%) asymptomatic patients without surgical criteria. Young age, serum calcium concentration, 24h urinary calcium, positive parathyroid imaging (either ultrasound or MIBI scan positive in 75% vs. 16.7%, P = 0.001) were predictors of parathyroid surgery. Almost all (94%) of patients were cured by PTx. Conclusions: Italian endocrinologists do not follow guidelines for the management of PHPT. Negative parathyroid imaging studies are strong predictors of a non-surgical approach. PTx is successful in almost all patients.