Diagnosis and treatment of Paget's disease of bone: position paper from the Italian Society of Osteoporosis, Mineral Metabolism and Skeletal Diseases (SIOMMMS).

INTRODUCTION: Paget's disease of bone is a focal skeletal disorder causing bone deformities and impairing bone quality. Despite the prevalence of asymptomatic cases is increasing, the progression of the disease can lead to invalidating complications that compromise the quality of life. Doubts on clinical and therapeutic management aspects exist, although beneficial effects of antiresorptive drugs, particularly bisphosphonates are known. However, limited information is available from randomized controlled trials on the prevention of disease complications so that somewhat contrasting positions about treatment indications between expert panels from the main scientific societies of metabolic bone diseases exist. This task force, composed by expert representatives appointed by the Italian Society of Osteoporosis, Mineral Metabolism and Skeletal Diseases and members of the Italian Association of Paget's disease of bone, felt the necessity for more specific and up to date indications for an early diagnosis and clinical management. METHODS: Through selected key questions, we propose evidence-based recommendations for the diagnosis and treatment of the disease. In the lack of good evidence to support clear recommendations, available information from the literature together with expert opinion of the panel was used to provide suggestions for the clinical practice. RESULTS AND CONCLUSION: Description of the evidence quality and support of the strength of the statements was provided on each of the selected key questions. The diagnosis of PDB should be mainly based on symptoms and the typical biochemical and radiological features. While treatment is mandatory to all the symptomatic cases at diagnosis, less evidence is available on treatment indications in asymptomatic as well as in previously treated patients in the presence of biochemical recurrence. However, given the safety and long-term efficacy of potent intravenous bisphosphonates such as zoledronate, a suggestion to treat most if not all cases at the time of diagnosis was released.

Bone health and body composition in transgender adults before gender-affirming hormonal therapy: data from the COMET study.

PURPOSE: Preliminary data suggested that bone mineral density (BMD) in transgender adults before initiating gender-affirming hormone therapy (GAHT) is lower when compared to cisgender controls. In this study, we analyzed bone metabolism in a sample of transgender adults before GAHT, and its possible correlation with biochemical profile, body composition and lifestyle habits (i.e., tobacco smoke and physical activity). METHODS: Medical data, smoking habits, phospho-calcic and hormonal blood tests and densitometric parameters were collected in a sample of 125 transgender adults, 78 Assigned Females At Birth (AFAB) and 47 Assigned Males At Birth (AMAB) before GAHT initiation and 146 cisgender controls (57 females and 89 males) matched by sex assigned at birth and age. 55 transgender and 46 cisgender controls also underwent a complete body composition evaluation and assessment of physical activity using the International Physical Activity Questionnaire (IPAQ). RESULTS: 14.3% of transgender and 6.2% of cisgender sample, respectively, had z-score values < -2 (p = 0.04). We observed only lower vitamin D values in transgender sample regarding biochemical/hormonal profile. AFAB transgender people had more total fat mass, while AMAB transgender individuals had reduced total lean mass as compared to cisgender people (53.94 ± 7.74 vs 58.38 ± 6.91, p < 0.05). AFAB transgender adults were more likely to be active smokers and tend to spend more time indoor. Fat Mass Index (FMI) was correlated with lumbar and femur BMD both in transgender individuals, while no correlations were found between lean mass parameters and BMD in AMAB transgender people. CONCLUSIONS: Body composition and lifestyle factors could contribute to low BMD in transgender adults before GAHT.

A universal UHPLC-CAD platform for the quantification of polysaccharide antigens.

Several glycoconjugate-based vaccines against bacterial infections have been developed and licensed for human use. Polysaccharide (PS) analysis and characterization is therefore critical to profile the composition of polysaccharide-based vaccines. For PS content quantification, the majority of Ultra High Performance Liquid Chromatography (UHPLC) methods rely on the detection of selective monosaccharides constituting the PS repeating unit, therefore requiring chemical cleavage and tailored development: only a few methods directly quantify the intact PS. The introduction of charged aerosol detector (CAD) technology has improved the response of polysaccharide analytes, offering greater sensitivity than other detector sources (e.g., ELSD). Herein, we report the development of a universal UHPLC-CAD method (UniQS) for the quantification and quality evaluation of polysaccharide antigens (e.g., Streptococcus Pneumoniae, Neisseria meningitidis and Staphylococcus aureus). This work laid the foundation for a universal UHPLC-CAD format that could play an important role in future vaccine research and development helping to reduce time, efforts, and costs.

Burden of disease and clinical targets in adult patients with X-linked hypophosphatemia. A comprehensive review.

X-linked hypophosphataemia (XLH) is a lifelong condition. Despite the mounting clinical evidence highlighting the long-term multi-organ sequelae of chronic phosphate wasting and consequent hypophosphatemia over the lifetime and the morbidities associated with adult age, XLH is still perceived as a paediatric disease. INTRODUCTION: Children who have XLH need to transition from paediatric to adult healthcare as young adults. While there is general agreement that all affected children should be treated (if the administration and tolerability of therapy can be adequately monitored), there is a lack of consensus regarding therapy in adults. METHODS: To provide guidance in both diagnosis and treatment of adult XLH patients and promote better provision of care for this potentially underserved group of patients, we review the available clinical evidence and discuss the current challenges underlying the transition from childhood to adulthood care to develop appropriate management and follow-up patterns in adult XLH patients. RESULTS AND CONCLUSIONS: Such a multi-systemic lifelong disease would demand that the multidisciplinary approach, successfully experienced in children, could be transitioned to adulthood care with an integration of specialized sub-disciplines to efficiently control musculoskeletal symptoms while optimizing patients' QoL. Overall, it would be desirable that transition to adulthood care could be a responsibility shared by the paediatric and adult XLH teams. Pharmacological management should require an adequate balance between the benefits derived from the treatment itself with complicated and long-term monitoring and the potential risks, as they may differ across age strata.

Vitamin D and disease severity in coronavirus disease 19 (COVID-19).

The role of 25-OH-vitamin D in the assessment of coronavirus disease 19 (COVID-19) has not been investigated. We sought to investigate the prevalence of 25-OH-vitamin D deficiency among COVID-19 patients, and to determine the associations between 25-OH-vitamin D status and the severity of the disease. We have conducted a retrospective observational study of COVID-19 patients admitted to the University of Verona Hospital Trust. Demographic, clinical and biochemical parameters were collected at hospital admission, and serum 25-OH-vitamin D levels were measured. The following outcomes were assessed: arterial partial oxygen pressure (PaO2); C-reactive protein (CRP); length of hospitalization; requirement of oxygen therapy; non-invasive ventilation (NIV); mechanical ventilation; and death. Among 61 patients enrolled, 72.1% was 25-OH-vitamin D deficient (<20 ng/mL) and 57.4% had 25-OHvitamin D <15 ng/mL. Patients with arterial PaO2 <60 mmHg had significantly lower mean 25-OH-vitamin D levels compared to patients with PaO2 ≥60 mmHg (13.3 ng/mL vs 20.4 ng/mL respectively, p=0.03). Vitamin D deficiency was associated with 3-fold higher risk of having arterial pO2 <60 mmHg. 25-OH-vitamin D deficiency was associated with increased CRP and dyspnea. 25-OH-vitamin D deficiency was associated with more severe systemic inflammatory response and respiratory failure in COVID-19 patients.

Providing high-quality care remotely to patients with rare bone diseases during COVID-19 pandemic.

During the COVID-19 outbreak, the European Reference Network on Rare Bone Diseases (ERN BOND) coordination team and Italian rare bone diseases healthcare professionals created the "COVID-19 Helpline for Rare Bone Diseases" in an attempt to provide high-quality information and expertise on rare bone diseases remotely to patients and healthcare professionals. The present position statement describes the key characteristics of the Helpline initiative, along with the main aspects and topics that recurrently emerged as central for rare bone diseases patients and professionals. The main topics highlighted are general recommendations, pulmonary complications, drug treatment, trauma, pregnancy, children and elderly people, and patient associations role. The successful experience of the "COVID-19 Helpline for Rare Bone Diseases" launched in Italy could serve as a primer of gold-standard remote care for rare bone diseases for the other European countries and globally. Furthermore, similar COVID-19 helplines could be considered and applied for other rare diseases in order to implement remote patients' care.

The civil liability of paediatric dentists in Italy. Trains of thought on novelties introduced by law n. 24/2017 ("Gelli-bianco" law).

AIM: This study offers an overview regarding news and main themes which have been introduced by Law n. 24/2017 (the so called "Gelli-Bianco" law) in Italy. The normative content deals with the features of civil liability for healthcare professionals. More specifically, this article is referred to the contractual and extra-contractual liability of paediatric dentists. Dentists often provide services combining healthcare and dental procedures as well as aesthetic activities. Thanks to the case law and doctrine tradition, the distinction between contracts of employment and contracts of work is clearly stated. This examination is focused on highlighting methods employed by paediatric dentists to prevent possible actions of suing for compensation.

Effects of PCSK9 inhibitors on LDL cholesterol, cardiovascular morbidity and all-cause mortality: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors determine a wide reduction of LDL cholesterol, greater than other lipid-lowering agents. The present meta-analysis is aimed at the assessment of PCSK9 inhibitors effect on LDL Cholesterol, cardiovascular morbidity and all-cause mortality. METHODS AND RESULTS: A Medline and Clinicaltrials.gov search for eligible studies until December 1, 2017, was performed. All randomized trials (> 12 weeks) comparing PCSK-9 inhibitors with placebo or active drugs were retrieved. Primary endpoints: (a) LDL cholesterol at endpoint; (b) Major cardiovascular events (MACE); (c) All-cause mortality. Data extraction was performed independently by two of the authors, and conflicts resolved by a third investigator. A total of 38 trials fulfilling the inclusion criteria were identified, with mean duration of 36.4 weeks. The reduction of LDL cholesterol at endpoint, versus placebo, ezetimibe, and high-dose statins was - 65.3 [- 69.6, - 60.9]%, - 57.7 [- 68.3;- 47.0]%, and - 34.5 [- 40.8;- 28.1]%, respectively, with alirocumab possibly showing a smaller effect than the other drugs of the class. Treatment with PCSK9 inhibitors was associated with a reduction in the incidence of MACE (Mantel-Haenszel Odds Ratio [MH-OR] 0.83 [0.78, 0.88]), with significant effects of alirocumab and evolocumab only. The number needed to treat for 2 years for preventing one event was 89. All-cause mortality and cardiovascular mortality were not reduced by treatment with PCSK-9 inhibitors (MH-OR 0.94 [0.84, 1.04] and 0.97[0.86;1.09]). CONCLUSIONS: PCSK-9 inhibitors are effective in reducing LDL cholesterol and the incidence of major cardiovascular events in high-risk patients. Bococizumab does not show significant effects on MACE. REGISTRATION NUMBER: PROSPERO-CRD42018087640.

Bioabsorbable implants for subtalar arthroereisis in pediatric flatfoot.

Flatfoot is a common condition in growing-age patients. Despite its common presentation, nowadays surgical indications and treatments are still debated. Arthroereisis is a widely used technique, and several implants designs have been proposed over time. Despite the good results shown in the literature, the main drawback of these techniques has always been the need for a second surgery for implant removal. Bioabsorbable devices have been introduced to overcome this necessity.Correct approach to the patient, indications and contraindications and available studies on bioabsorbable implants for subtalar arthroereisis in pediatric flatfoot were analyzed in this narrative review. Even if only a few studies have been published in the literature, bioabsorbable implants showed good clinical results comparable to non-absorbable implants and with a rare necessity for implant removal or revision. When correct indications and proper surgical technique are followed, arthroereisis with bioabsorbable implants appears to be an effective solution for the treatment of pediatric flexible flatfoot.

Glucagon-like peptide-1 receptor agonists and atrial fibrillation: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: The pharmacological stimulation of GLP-1 receptors is associated with an increase in heart rate. A pooled analysis of patient-level data from phase III trials with albiglutide revealed a significant increase in the risk of atrial fibrillation. Aim of the present meta-analysis is to summarize all available evidence on the effects of individual GLP-1 receptor agonists (RA), and of the whole class, on the incidence of atrial fibrillation. METHODS: A Medline search for GLP-1 RA (exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, or semaglutide) was performed, collecting all randomized clinical trials with a duration ≥12 weeks, enrolling patients with type 2 diabetes and comparing a GLP-1 RA with placebo or any other non-GLP-1 RA drug. RESULTS: Of the 113 trials fulfilling the inclusion criteria, 19 did not report information on atrial fibrillation, whereas 63 reported zero events in all treatment groups. In the remaining trials (enrolling 17,966 and 15,305 patients in GLP-1 RA and comparator arms, respectively, 55.3% women, with a mean age of 57.0 ± 3.8 years), treatment with GLP-1 RA was not associated with a significant increase in the incidence of atrial fibrillation [Mantel-Haenszel OR (95% CI) 0.87 (0.71-1.05), p = 0.15]. CONCLUSIONS: In conclusion, available data suggest that GLP-1 RA is not associated with atrial fibrillation, with the only possible exception of albiglutide. Newly onset atrial fibrillation deserves to be investigated as an event of special interest in future trials with GLP-1 RA.

Fresh osteochondral allotransplants: Outcomes, failures and future developments.

Osteochondral allografts are used to treat many different conditions as acute traumatic large-sized lesions, degenerative osteoarthritis, osteochondritis dissecans, avascular necrosis or in case of failure of previous procedures particularly in young patients for whom primary prosthesis is not desirable. Fresh allografts present the advantage of having mature viable hyaline cartilage, not causing donor morbidity, allowing the restoration of even large defects in a single surgical session. Conversely, they could account for risks of disease transmission, immunologic reactions, and for limited availability. The present review aimed to analyze published studies of the last decade in which patients received fresh osteochondral allografts by dividing them for knee or ankle regenerative purposes. We wish to report the observed failure rates and particularly to collect any other reported side effect or outcome for identifying major problems and limits linked to the procedure and for delineating possible future researches and approaches. The overall success rates resulted ranging from 5.3% to 48.3% in the ankle at a mean follow up of 3.3 years and from 0% to 85.7% in the knee at a mean follow up of 7.1 years. Among other outcomes, occurrence or progression of arthritis, osteolysis, graft instability, fractures, nonunions, edema and infections were recorded. Overall, the lack of well designed randomized and controlled clinical trials, of immunological determination of the anti-donor antibodies development and of local and systemic biomarkers to detect reaction to the graft seems to be the major drawback. Improvements in these limiting factors might be desirable in order to enhance the clinical scenario of a well-established and successful procedure to give, especially for young patients, a real regeneration of the joint.

Bipolar fresh total osteochondral allograft in the ankle: Is it a successful long-term solution?

INTRODUCTION: Severe post-traumatic ankle arthritis poses a reconstructive challenge in young and active patients. Although technically demanding and despite unsolved immunological issues, bipolar fresh total osteochondral allograft (BFTOA) represent an intriguing option to arthrodesis and prosthetic replacement. The purpose of this paper is to evaluate the outcomes of a series of 48 ankle BFTOA at 10 years follow up and to investigate the rate of survival long term. METHODS: 58 patients underwent BFTOA, of these 48 were available for follow up. The allograft was prepared with the help of specifically designed jigs and the surgery was performed using either a lateral or a direct anterior approach. Patients were evaluated clinically and radiographically preoperatively, and at a mean 121±18months of follow-up. RESULTS: The AOFAS score improved from 31±11 pre operatively, to 65±25 at the last (p<0.0005). Fourteen failures occurred, with 70.8% allograft rate of survival. All the surviving allografts showed a reduction of the ankle joint movement, still associated with a satisfactory clinical result. CONCLUSION: The use of BFTOA represents an intriguing option to arthrodesis or arthroplasty. A satisfactory clinical result associated to a good movement of the transplanted joint is to be expected up to short-mid-term, overtime. Long term, the range of motion (ROM) is progressively decreased up to spontaneous arthrodesis in some cases, still the joint results pain free and patient's perception is of a well functioning ankle. A deeper knowledge of the immunological behavior of transplanted cartilage is needed in order to improve the durability of this fascinating technique.

Association between low C-peptide and fragility fractures in postmenopausal women without diabetes.

PURPOSE: C-peptide has been shown to exert several, previously unknown, biological effects. A recent cross-sectional study demonstrated an association between low C-peptide serum levels and low lumbar bone density of postmenopausal women not affected by diabetes. To date, very little research attention has been directed toward the association between C-peptide and osteoporotic fractures. To contribute toward filling this gap, we investigated the association between C-peptide and fractures in postmenopausal women. METHODS: A cohort of 133 non-diabetic postmenopausal women with and without a history of fractures was evaluated in this cross-sectional investigation. Standardized interviews were performed to gather information on the patients' fracture history. All of the participants underwent a bone mineral density assessment by DXA, radiographs, and a serum C-peptide measurement. RESULTS: Thirty-four women presented fractures. Bivariate analysis revealed an inverse correlation between C-peptide and fractures (r = -0.27, p = 0.002). A significant difference in mean C-peptide levels was also found between women with vs. without fractures (p = 0.01, adjusted for age, BMI and glucose). Logistic regression analysis showed that C-peptide levels, femoral and vertebral BMD were all negatively associated with fracture status (B = -1.097, ES = 0.401, p = 0.006, 95% CI 0.15-0.73; B = -15.6, SE = 4.17, p < 0.001, CI 0.001-0.002; B = -24.8, SE = 5.23, p < 0.001, CI 0001-0.002; respectively). CONCLUSIONS: This study confirms an inverse association between serum C-peptide levels and a history of fractures in postmenopausal women without diabetes. These results suggest that C-peptidemay exert an effect on bone mineral density. However, further large-scale studies are needed to corroborate this finding and investigate the potential underlying mechanisms involved.

Testing the Efficacy of Contrast-Enhanced Ultrasound in Detecting Transplant Rejection Using a Murine Model of Heart Transplantation.

One of the key unmet needs to improve long-term outcomes of heart transplantation is to develop accurate, noninvasive, and practical diagnostic tools to detect transplant rejection. Early intragraft inflammation and endothelial cell injuries occur prior to advanced transplant rejection. We developed a novel diagnostic imaging platform to detect early declines in microvascular perfusion (MP) of cardiac transplants using contrast-enhanced ultrasonography (CEUS). The efficacy of CEUS in detecting transplant rejection was tested in a murine model of heart transplants, a standard preclinical model of solid organ transplant. As compared to the syngeneic groups, a progressive decline in MP was demonstrated in the allografts undergoing acute transplant rejection (40%, 64%, and 92% on days 4, 6, and 8 posttransplantation, respectively) and chronic rejection (33%, 33%, and 92% on days 5, 14, and 30 posttransplantation, respectively). Our perfusion studies showed restoration of MP following antirejection therapy, highlighting its potential to help monitor efficacy of antirejection therapy. Our data suggest that early endothelial cell injury and platelet aggregation contributed to the early MP decline observed in the allografts. High-resolution MP mapping may allow for noninvasive detection of heart transplant rejection. The data presented have the potential to help in the development of next-generation imaging approaches to diagnose transplant rejection.

Congenital forward shoulder with clavicle hypoplasia: surgical lengthening by intercalary graft positioning and plate fixation.

BACKGROUND: Congenital forward shoulder with clavicular hypoplasia is a rare disease which can be caused by an alteration of clavicular development in such a way that the clavicles are short. Symptoms are often absent; in most cases the main problem is represented by the cosmetic implications. There is no general consensus about the correct management, and surgery is the only way to correct the deformity. MATERIALS AND METHODS: The aim of the study is to describe a new surgical treatment in patients with congenital forward shoulder and clavicular hypoplasia. In 2010, three patients suffering from bilateral congenital forward shoulder were managed surgically by a intercalary graft positioning with plate fixation aimed at the elongation of the clavicles. RESULTS: Patients were followed by up to 2 years. All the patients treated were satisfied with the results, regarding the resolution of mild pain, but especially from the cosmetic point of view. CONCLUSION: The intercalary graft positioning was found to be easy to perform and allowed an elongation of the clavicles with immediate stability.

Minimally-invasive treatment of calcaneal fractures: A review of the literature and our experience.

The optimal treatment of calcaneal fractures (CF) is currently controversial and is still under debate. It is well established that conservative treatment of these fractures is associated with poor results. Several surgical techniques are described in the literature; however, there is no consensus on which of these is more effective. The main goals of surgery are to restore the subtalar joint congruence, and calcaneal width, height, shape and alignment, thus avoiding medial and lateral impingement and enabling the patient to resume a normal lifestyle. ORIF is the most popular technique for these fractures, but it is associated with high rates of wound complications, hardware failure and infections. Several minimally-invasive techniques have been developed recently for the treatment of CF, with the common aim to be as simple, effective and inexpensive as possible and to reduce surgical times, complications and length of hospital stay.

Nephrolithiasis, bone mineral density, osteoporosis, and fractures: a systematic review and comparative meta-analysis.

Our meta-analysis demonstrates that people with nephrolithiasis have decreased bone mineral density, an increased odds of osteoporosis, and potentially an elevated risk of fractures. INTRODUCTION: People with nephrolithiasis might be at risk of reduced bone mineral density (BMD) and fractures, but the data is equivocal. We conducted a meta-analysis to investigate if patients with nephrolithiasis have worse bone health outcomes (BMD), osteoporosis, and fractures versus healthy controls (HCs). METHODS: Two investigators searched major databases for articles reporting BMD (expressed as g/cm2 or a T- or Z-score), osteoporosis or fractures in a sample of people with nephrolithiasis, and HCs. Standardized mean differences (SMDs), 95 % confidence intervals (CIs) were calculated for BMD parameters; in addition odds (ORs) for case-control and adjusted hazard ratios (HRs) in longitudinal studies for categorical variables were calculated. RESULTS: From 1816 initial hits, 28 studies were included. A meta-analysis of case-control studies including 1595 patients with nephrolithiasis (mean age 41.1 years) versus 3402 HCs (mean age 40.2 years) was conducted. Patients with nephrolithiasis showed significant lower T-scores values for the spine (seven studies; SMD = -0.69; 95 % CI = -0.86 to -0.52; I 2 = 0 %), total hip (seven studies; SMD = -0.82; 95 % CI = -1.11 to -0.52; I 2 = 72 %), and femoral neck (six studies; SMD = -0.67; 95 % CI = --1.00 to -0.34; I 2 = 69 %). A meta-analysis of the case-controlled studies suggests that people with nephrolithiasis are at increased risk of fractures (OR = 1.15, 95 % CI = 1.12-1.17, p < 0.0001, studies = 4), while the risk of fractures in two longitudinal studies demonstrated trend level significance (HR = 1.31, 95 % CI = 0.95-1.62). People with nephrolithiasis were four times more likely to have osteoporosis than HCs (OR = 4.12, p < 0.0001). CONCLUSIONS: Nephrolithiasis is associated with lower BMD, an increased risk of osteoporosis, and possibly, fractures. Future screening/preventative interventions targeting bone health might be indicated.

Guidelines for the diagnosis, prevention and management of osteoporosis.

Osteoporosis poses a significant public health issue. National Societies have developed Guidelines for the diagnosis and treatment of this disorder with an effort of adapting specific tools for risk assessment on the peculiar characteristics of a given population. The Italian Society for Osteoporosis, Mineral Metabolism and Bone Diseases (SIOMMMS) has recently revised the previously published Guidelines on the diagnosis, riskassessment, prevention and management of primary and secondary osteoporosis. The guidelines were first drafted by a working group and then approved by the board of SIOMMMS. Subsequently they received also the endorsement of other major Scientific Societies that deal with bone metabolic disease. These recommendations are based on systematic reviews of the best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on leading experts' experience and opinion, and on good clinical practice. The osteoporosis prevention should be based on the elimination of specific risk factors. The use of drugs registered for the treatment of osteoporosis are recommended when the benefits overcome the risk, and this is the case only when the risk of fracture is rather high as measured with variables susceptible to pharmacological effect. DeFRA (FRAX® derived fracture risk assessment) is recognized as a useful tool for easily estimate the long-term fracture risk. Several secondary forms of osteoporosis require a specific diagnostic and therapeutic management.

OCCUPATIONAL EXPOSURE TO EXTERNAL RADIATION IN SWITZERLAND.

Individual monitoring for both external and internal exposures is well regulated in Switzerland. The article gives an overview on the occupational exposure to external radiation of workers based on the data collected in the Swiss national dose registry (NDR) in 2013. The NDR records the monthly doses of radiation workers since the introduction of ICRP 60 recommendations and is manifested in the Swiss ordinance since 1994. Annual dose limits for effective dose are typically exceeded once a year in Switzerland, mostly in medicine. The NDR is a useful optimisation tool to identify and characterise areas with the highest exposures. While exceeded dose limits were often related to accidental acute exposure in the past, they are now more related to continuous exposure during normal work, especially in medicine.

PATHOLOGIC AND IMPENDING FRACTURES: BIOLOGICAL AND CLINICAL ASPECTS.

Bone metastases from carcinomas are epidemiologically rising because of the increased survival rate of oncologic patients, related to several factors such as improvement of primary and secondary screening, advancement of medical research and technology and the better understanding of mechanisms underlying bone metastases origination from primary tumor. Skeletal Related Events (SREs) can seriously affect quality of life in patients with metastatic disease. These events include the necessity of radiotherapy or bone surgery, malignant hypercalcemia, pathologic fractures and spinal cord compression. Among the SREs, pathologic fractures are the most disabling events and represent an emergency in these delicate patients. A pathologic fracture is defined as a fracture that occurs at the level of a pre-existing bone lesion (that is often a tumor), spontaneously or as the result of low-energy trauma (1). The pre-existence of the metastatic lesion in the bone, its evaluation and the assessment of progression can make these complications predictable and preventable. Pathologic fractures imply several severe consequences, including patient immobilization (in the case of fractures involving the lower limbs), loss of autonomy, anaemia, need of blood transfusion, discontinuation of medical therapies or radiotherapy and protracted hospitalization. Secondary effects of prolonged immobilization and loss of autonomy further lengthen this list of complications in patients who are already significantly limited in their activities. In the present paper, the authors present a review on the main aspects involved in bone metastastic disease: biology, quality of life, economic impact and survival.