Monitoring Huntington's Disease Mortality across a 30-Year Period: Geographic and Temporal Patterns.

BACKGROUND: Huntington's disease (HD) is a progressive neurodegenerative condition characterized by chorea, dystonia, behavioral disturbances and cognitive decline. The aim of this study is to assess temporal and spatial changes on mortality attributable to HD over 30 years in Spain. METHODS: HD data were extracted from the nationwide mortality registry for the period 1984-2013. Annual and 5-year gender- and age-specific rates adjusted for the standard European population were calculated. Geographic analysis was performed by districts from 1999 through 2013, and then estimated standardized mortality ratios (SMRs) and smoothed SMRs. RESULTS: There were 1,556 HD-related deaths across the study period. An increasing trend in age-adjusted HD mortality was in evidence, specifically from 1994 through 1998. On a year-by-year basis, age-adjusted mortality rates increased from 0.076 per 100,000 population in 1984 to 0.157 in 2013. Geographical differences among districts were evident in specific areas and in the southwest of Spain with a significantly higher HD mortality risk. CONCLUSION: HD mortality rising trends in Spain might be attributable to improvements in diagnosis leading to a rise in prevalence. Geographical variability in HD mortality could be related to regional differences in disease prevalence, health-care disparities, or other factors which call for in-depth assessment in future studies.

Association between residential proximity to environmental pollution sources and childhood renal tumors.

BACKGROUND: Few risk factors for childhood renal tumors are well established. While a small fraction of cases might be attributable to susceptibility genes and congenital anomalies, the role of environmental factors needs to be assessed. OBJECTIVES: To explore the possible association between residential proximity to environmental pollution sources (industrial and urban areas, and agricultural crops) and childhood renal cancer, taking into account industrial groups and toxic substances released. METHODS: We conducted a population-based case-control study of childhood renal cancer in Spain, including 213 incident cases gathered from the Spanish Registry of Childhood Tumors (period 1996-2011), and 1278 controls individually matched by year of birth, sex, and region of residence. Distances were computed from the respective subject's residences to the 1271 industries, the 30 urban areas with ≥75,000 inhabitants, and the agricultural crops located in the study area. Using logistic regression, odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance to pollution sources were calculated, with adjustment for matching variables and socioeconomic confounders. RESULTS: Excess risk (OR; 95%CI) of childhood renal tumors was observed for children living near (≤2.5km) industrial installations as a whole (1.97; 1.13-3.42) - particularly glass and mineral fibers (2.69; 1.19-6.08), galvanization (2.66; 1.14-6.22), hazardous waste (2.59; 1.25-5.37), ceramic (2.35; 1.06-5.21), surface treatment of metals (2.25; 1.24-4.08), organic chemical industry (2.22; 1.15-4.26), food and beverage sector (2.19; 1.18-4.07), urban and waste-water treatment plants (2.14; 1.07-4.30), and production and processing of metals (1.98; 1.03-3.82) -, and in the proximity of agricultural crops (3.16; 1.54-8.89 for children with percentage of crop surface ≥24.35% in a 1-km buffer around their residences). CONCLUSIONS: Our study provides some epidemiological evidence that living near certain industrial areas and agricultural crops may be a risk factor for childhood renal cancer.

Residential proximity to environmental pollution sources and risk of rare tumors in children.

BACKGROUND: Few epidemiologic studies have explored risk factors for rare tumors in children, and the role of environmental factors needs to be assessed. OBJECTIVES: To ascertain the effect of residential proximity to both industrial and urban areas on childhood cancer risk, taking industrial groups into account. METHODS: We conducted a population-based case-control study of five childhood cancers in Spain (retinoblastoma, hepatic tumors, soft tissue sarcomas, germ cell tumors, and other epithelial neoplasms/melanomas), including 557 incident cases from the Spanish Registry of Childhood Tumors (period 1996-2011), and 3342 controls individually matched by year of birth, sex, and region of residence. Distances were computed from the residences to the 1271 industries and the 30 urban areas with ≥75,000 inhabitants located in the study area. Using logistic regression, odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance to industrial and urban pollution sources were calculated, with adjustment for matching variables and socioeconomic confounders. RESULTS: Children living near industrial and urban areas as a whole showed no excess risk for any of the tumors analyzed. However, isolated statistical associations (OR; 95%CI) were found between retinoblastoma and proximity to industries involved in glass and mineral fibers (2.49; 1.01-6.12 at 3km) and organic chemical industries (2.54; 1.10-5.90 at 2km). Moreover, soft tissue sarcomas registered the lower risks in the environs of industries as a whole (0.59; 0.38-0.93 at 4km). CONCLUSIONS: We have found isolated statistical associations between retinoblastoma and proximity to industries involved in glass and mineral fibers and organic chemical industries.

Agricultural crop exposure and risk of childhood cancer: new findings from a case-control study in Spain.

BACKGROUND: Childhood cancer is the main cause of disease-related death in children in Spain. Although little is known about the etiology, environmental factors are potential explanations for a fraction of the cases. Previous studies have shown pesticides to be associated with childhood cancer. The difficulty of collecting personal environmental exposure data is an important limitation; this lack of information about pesticides motivates the development of new methods to subrogate this exposure. We developed a crop exposure index based on geographic information to study the relationship between exposure to different types of crops and risk of childhood tumors. METHODS: We conducted a population-based case-control study of childhood cancer covering 3350 cases and 20,365 controls in two Spanish regions. We used CORINE Land Cover to obtain data about agricultural land use. We created a 1 km buffer around every child and calculated the percentage of crop surface within the buffer (Global Crop Index) for total crops and for individual types of crops. We fitted mixed multiple unconditional logistic regression models by diagnostic group. RESULTS: We found excess of risk among children living in the proximity of crops. For total crops our results showed excesses of risk for almost all diagnostic groups and increasing risk with increasing crop index value. Analyses by region and individual type of crop also showed excess of risk. CONCLUSION: The results suggest that living in the proximity of cultivated land could be a risk factor for several types of cancer in children.

Childhood leukemia and residential proximity to industrial and urban sites.

BACKGROUND: Few risk factors for the childhood leukemia are well established. While a small fraction of cases of childhood leukemia might be partially attributable to some diseases or ionizing radiation exposure, the role of industrial and urban pollution also needs to be assessed. OBJECTIVES: To ascertain the possible effect of residential proximity to both industrial and urban areas on childhood leukemia, taking into account industrial groups and toxic substances released. METHODS: We conducted a population-based case-control study of childhood leukemia in Spain, covering 638 incident cases gathered from the Spanish Registry of Childhood Tumors and for those Autonomous Regions with 100% coverage (period 1990-2011), and 13,188 controls, individually matched by year of birth, sex, and autonomous region of residence. Distances were computed from the respective subject's residences to the 1068 industries and the 157 urban areas with ≥10,000 inhabitants, located in the study area. Using logistic regression, odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance to industrial and urban pollution sources were calculated, with adjustment for matching variables. RESULTS: Excess risk of childhood leukemia was observed for children living near (≤2.5 km) industries (OR=1.31; 95%CI=1.03-1.67) - particularly glass and mineral fibers (OR=2.42; 95%CI=1.49-3.92), surface treatment using organic solvents (OR=1.87; 95%CI=1.24-2.83), galvanization (OR=1.86; 95%CI=1.07-3.21), production and processing of metals (OR=1.69; 95%CI=1.22-2.34), and surface treatment of metals (OR=1.62; 95%CI=1.22-2.15) - , and urban areas (OR=1.36; 95%CI=1.02-1.80). CONCLUSIONS: Our study furnishes some evidence that living in the proximity of industrial and urban sites may be a risk factor for childhood leukemia.

Mortality of congenital osteochondrodysplasias: a nationwide registry-based study.

Osteochondrodysplasias are a heterogeneous group of more than 200 entities, characterized by abnormalities of cartilage, bone growth, and skeletal development. The aim of this study was to assess temporal and spatial changes in overall mortality due to these disorders in Spain, using data from a nationwide registry. Annual deaths showing osteochondrodysplasias as the underlying cause of death were selected using the International Classification of Diseases-9th revision (ICD-9) codes for the period 1981 through 1998, and ICD-10 codes for the period 1999 through 2008. Age-adjusted mortality rates were calculated by sex, and geographic analysis was performed by municipality. A total of 679 deaths were recorded (53% men). Age-adjusted mortality rates went from 0.09 (0.06, 0.12) per 100,000 population in 1981 to 0.05 (0.03, 0.08) per 100,000 population in 2008. A changing trend in the age-standardized mortality rate was in evidence, with an annual increase of 2.4% (-0.4, 5.2) from 1981 to 1994, and an annual decrease of -7.3% (-10.9, -3.5) from 1995 onwards. Geographic analysis showed some places situated in the west and south of Spain with greater risk of mortality. There is a need to identify risk factors and to increase overall knowledge about the life expectancy and epidemiology of osteochondrodysplasias.

Epidemiology of hereditary ataxias in Spain: hospital discharge registry and population-based mortality study.

BACKGROUND: Hereditary ataxias (HA) comprise a group of genetically heterogeneous rare diseases. As important public health problems to be monitored, this study analyses the morbimortality of HA in Spain. METHODS: Data were extracted from the national death index (1981-2008), using the International Classification of Diseases (ICD) 9th revision code 334 until 1998, and 10th revision code G11 from 1999 onwards. ICD-9 codes were then selected from the national discharge dataset (1998-2007). Age-adjusted morbidity and mortality rates were obtained by gender and 5-year period. RESULTS: Of the 610 HA deaths from 1981 to 2008, 277 corresponded to Friedreich's ataxia (45.4%) and 333 (54.6%) to other and unspecified ataxias (non-Friedreich group). Both groups showed an increase in mortality trend, which was more pronounced in males from 1985-1989 to 1990-1994. Geographical distribution of mortality revealed higher risk for males, mainly in the north of Spain. A total of 5,341 HA hospitalisations were identified from 1998 to 2007. The average annual age-adjusted hospitalisation rate was 1.19 per 100,000 population, with a rising trend. CONCLUSION: This increase in morbidity and mortality, coupled with the slight interprovincial differences, indicate that more attention should be paid to these rare diseases by public authorities and society alike.

[Is there a place in primary care for rare diseases? The case of fibrodysplasia ossificans progressiva]. / ¿Hay lugar en atención primaria para las enfermedades poco frecuentes? El caso de la fibrodisplasia osificante progresiva.

Fibrodysplasia ossificans progressiva is one of the most devastating constitutional diseases of the bone, and may be a valid example to establish the role of Primary Care in the care of rare diseases. Although rare diseases usually present with marked anomalies, they can mimic signs and symptoms of common disorders, with the risk of going unnoticed. For this reason, all health professionals should proceed with a reasonable suspicion when confronted with a patient with an apparently common disease with atypical symptoms and a non-conventional progress. The care given by the Primary Care team along with other health care services are fundamental in the integrated and individualised follow-up. The quality of care in rare diseases must not be inferior to that provided to the other chronic diseases, since, besides being a requirement of justice and fairness, these patients are, in essence, the "paradigm of chronicity".

Implications of a new radiological approach for the assessment of Paget disease.

In the present study, we quantified the proportion of skeletal involvement of Paget disease of bone (PDB) not captured by an abdominal X-ray. We also analyzed extension and severity over time and tested the hypothesis that X-rays from selected areas could replace bone scans for mapping PBD. We examined whole skeletal (99m)TC-MDP bone scans from 208 consecutive untreated patients. Pagetic bones included in an abdominal X-ray were delimited; disease extension and activity were calculated using Coutris's index as well as Renier's index and serum alkaline phosphatase (AP) values, respectively. The study period (1965-2007) was divided into quartiles according to the date of the diagnosis. The percentage of patients with PDB captured by an abdominal X-ray was 79 % (95 % CI 74-85 %). In the last quartile vs. the first quartile, PDB was diagnosed at a more advanced age (67 ± 11 vs. 57 ± 9 years, respectively), with a lower median extension (4 vs. 7) and similar median activity (32 vs. 35) but less activity through median AP values (183 vs. 485 UI/L). The skeletal locations to X-ray in order to capture up to 93 % of PDB extension were the abdomen, skull with facial bones, and both tibias. In conclusion, one-fifth of patients are underdiagnosed when assessing prevalence of PDB by an X-ray of the abdomen, and there is a secular trend to presentation in older patients with a decreasing extension of the disease. A set of X-rays that includes abdomen, skull with facial bones, and both tibias provides a reliable alternative to bone scans.

Increase in motor neuron disease mortality in Spain: temporal and geographical analysis (1990-2005).

The aim of this study was to assess the trend of motor neuron disease mortality in Spain from 1990 to 2005, and to ascertain the existence of geographical differences in mortality rates. MND deaths are registered by the National Statistics Institute of Spain ­ International Classification of Diseases (ICD) codes ICD9 335.2 (1990-1998) and ICD10 G12.2 (1999-2005). Annual sex- and age-specific rates, as well as rates adjusted for the standard European population were obtained. Provincial standardized mortality ratios (SMRs) were calculated for the study period. Respective provincial SMRs were smoothed with data from adjacent provinces using a Poisson model. Results showed that MND mortality increased in Spain from 1990 to 2005. Geographical differences between provinces were evident throughout the study period. In general, risk of death due to MND was higher in regions lying to the north of Spain. In conclusion, the temporal and geographical variability observed might be explained by genetic factors, differences in environmental exposures and the possible influence of the type of medical care and treatment received. Mortality depends also on health service quality and diagnostic validity. All these factors may play a very important role in analysis of MND mortality in Spain, and the contribution of each of these will have to be examined in depth by ad hoc studies.

Osteochondral diseases and fibrodysplasia ossificans progressiva.

Osteochondrodysplasias like thanatophoric dysplasia, osteogenesis imperfecta, achondroplasia, and other genetic skeletal disorders like fibrodysplasia ossificans progressiva are infrequently seen in clinical practice. In cases of sporadic achondroplasia as well as in fibrodysplasia ossificans progressiva, there is a strong association with paternal age, a relationship that is less evident in other genetic osteochondral diseases. No other constitutional or environmental factor has proven to be associated with these disorders. The use of prenatal ultrasonography as a routine component of prenatal care is crucial in the early suspicion of osteochondrodysplasias whereas definitive diagnosis is usually obtained by pre-natal molecular analysis. In the case of fibrodysplasia ossificans progressiva, recognition of congenital great toe malformations associated with rapidly-appearing soft tissue swelling is sufficient to make the proper clinical diagnosis, which can be confirmed by genetic testing. Large regional centres will improve diagnosis performance, provide accurate genetic counselling, and ensure an integral assistance for these often severe and incapacitating conditions.

[The ethical aspects of population screening programme of rare diseases]. / Recomendaciones sobre los aspectos éticos de los programas de cribado de población para enfermedades raras.

The Committee on Ethics of the Instituto de Investigación de Enfermedades Raras (CEIIER) of the Spanish National Institute of Health Carlos III, presents this article dealing with ethical guidelines regarding the implementation of screening population programmes with special emphasis on genetic screening. After a critical review it has been addressed 24 recommendations concerning 14 topics: evaluation of the opportunity of the programme, including ethical analysis besides scientific evidences and cost/benefits issues; the need to differentiate between research and public health intervention and to built a specific and comprehensive programme; the creation of an interdisciplinary working group which control its implementation and prepare a protocol including justification, development, therapeutic or preventive actions and follow-up activities; the review of the programme by an independent Ethical committee; the guarantee of the voluntary, universal and equitable population access, which requires sufficient information on the programme and their specific relevant facts, as incidental detection of heterozygous state in minors in newborn screening and the relevance of non directive genetic counselling specially in prenatal screening offered to pregnant women; considerations regarding future uses of samples for research purposes; total quality and periodic programme evaluation; guarantee of personal data confidentiality and the conflict of interest statement of the members of all the Committees involved in the programme.

Development of Macrocycle Kinase Inhibitors for ALK2 Using Fibrodysplasia Ossificans Progressiva-Derived Endothelial Cells.

Fibrodysplasia ossificans progressiva (FOP) is an extremely rare congenital form of heterotopic ossification (HO), caused by heterozygous mutations in the activin A type I receptor (ACVR1), that encodes the bone morphogenetic protein (BMP) type I receptor ALK2. These mutations enable ALK2 to induce downstream signaling in response to activins, thereby turning them into bone-inducing agents. To date, there is no cure for FOP. The further development of FOP patient-derived models may contribute to the discovery of novel biomarkers and therapeutic approaches. Nevertheless, this has traditionally been a challenge, as biopsy sampling often triggers HO. We have characterized peripheral blood-derived endothelial colony-forming cells (ECFCs) from three independent FOP donors as a new model for FOP. FOP ECFCs are prone to undergo endothelial-to-mesenchymal transition and exhibit increased ALK2 downstream signaling and subsequent osteogenic differentiation upon stimulation with activin A. Moreover, we have identified a new class of small molecule macrocycles with potential activity against ALK2 kinase. Finally, using FOP ECFCs, we have selected OD36 and OD52 as potent inhibitors with excellent kinase selectivity profiles that potently antagonize mutant ALK2 signaling and osteogenic differentiation. We expect that these results will contribute to the development of novel ALK2 clinical candidates for the treatment of FOP. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Risk factors for central nervous system tumors in children: New findings from a case-control study.

BACKGROUND: Central nervous system tumors (CNS) are the most frequent solid tumor in children. Causes of CNS tumors are mainly unknown and only 5% of the cases can be explained by genetic predisposition. We studied the effects of environmental exposure on the incidence of CNS tumors in children by subtype, according to exposure to industrial and/or urban environment, exposure to crops and according to socio-economic status of the child. METHODS: We carried out a population-based case-control study of CNS tumors in Spain, covering 714 incident cases collected from the Spanish Registry of Childhood Tumors (period 1996-2011) and 4284 controls, individually matched by year of birth, sex, and autonomous region of residence. We built a covariate to approximate the exposure to industrial and/or urban environment and a covariate for the exposure to crops (GCI) using the coordinates of the home addresses of the children. We used the 2001 Census to obtain information about socio-economic status (SES). We fitted logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (95%CIs). RESULTS: The results for all CNS tumors showed an excess risk (OR = 1.37; 95%CI = 1.09-1.73) for SES, i.e., children living in the least deprived areas had 37% more risk of CNS tumor than children living in the most deprived areas. For GCI, an increase of 10% in crop surface in the 1-km buffer around the residence implied an increase of 22% in the OR (OR = 1.22; 95%CI = 1.15-1.29). Children living in the intersection of industrial and urban areas could have a greater risk of CNS tumors than children who live outside these areas (OR = 1.20; 95%CI = 0.82-1.77). Living in urban areas (OR = 0.90; 95%CI = 0.65-1.24) or industrial areas (OR = 0.96; 95%CI = 0.81-1.77) did not seem to increase the risk for all CNS tumors together. By subtype, Astrocytomas, Intracranial and intraspinal embryonal tumors, and other gliomas showed similar results. CONCLUSION: Our results suggest that higher socioeconomic status and exposure to crops could increase the risk of CNS tumors in children.

Risk of bone tumors in children and residential proximity to industrial and urban areas: New findings from a case-control study.

Few epidemiologic studies have explored risk factors for bone tumors in children, and the role of environmental factors needs to be analyzed. Our objective was to ascertain the association between residential proximity to industrial plants and urban areas and risk of bone tumors in children, taking into account industrial groups and toxic pollutants released. A population-based case-control study of childhood bone cancer in Spain was carried out, covering 114 incident cases obtained from the Spanish Registry of Childhood Tumors (between 1996 and 2011), and 684 controls individually matched by sex, year of birth, and autonomous region of residence. Distances from the subject's residences to the 1271 industries and the 30 urban areas (towns) with ≥75,000 inhabitants located in the study area were computed. Unconditional logistic regression models were fitted to estimate odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance (from 1km to 3km) to industrial and urban areas, with adjustment for matching variables and sociodemographic indicators. Excess risk (OR; 95%CI) of bone tumors in children was detected for children close to industrial facilities as a whole (2.33; 1.17-4.63 at 3km) - particularly surface treatment of metals (OR=2.50; 95%CI=1.13-5.56 at 2km), production and processing of metals (OR=3.30; 95%CI=1.41-7.77 at 2.5km), urban waste-water treatment plants (OR=4.41; 95%CI=1.62-11.98 at 2km), hazardous waste (OR=4.63; 95%CI=1.37-15.61 at 2km), disposal or recycling of animal waste (OR=4.73; 95%CI=1.40-15.97 at 2km), cement and lime (OR=3.89; 95%CI=1.19-12.77 at 2.5km), and combustion installations (OR=3.85; 95%CI=1.39-10.66 at 3km)-, and urban areas (4.43; 1.80-10.92). These findings support the need for more detailed exposure assessment of certain toxics released by these facilities.

Risk of neuroblastoma and residential proximity to industrial and urban sites: A case-control study.

BACKGROUND: Neuroblastoma is the most common extracranial solid tumor in children but its etiology is not clearly understood. While a small fraction of cases might be attributable to genetic factors, the role of environmental pollution factors needs to be assessed. OBJECTIVES: To ascertain the effect of residential proximity to both industrial and urban areas on neuroblastoma risk, taking into account industrial groups and toxic substances released. METHODS: We conducted a population-based case-control study of neuroblastoma in Spain, including 398 incident cases gathered from the Spanish Registry of Childhood Tumors (period 1996-2011), and 2388 controls individually matched by year of birth, sex, and region of residence. Distances were computed from the respective subject's residences to the 1271 industries and the 30 urban areas with ≥75,000 inhabitants located in the study area. Using logistic regression, odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance (from 1km to 5km) to industrial and urban pollution sources were calculated, with adjustment for matching variables and socioeconomic confounders. RESULTS: Excess risk (OR; 95%CI) of neuroblastoma was detected for the intersection between industrial and urban areas: (2.52; 1.20-5.30) for industrial distance of 1km, and (1.99; 1.17-3.37) for industrial distance of 2km. By industrial groups, excess risks were observed near 'Production of metals' (OR=2.05; 95%CI=1.16-3.64 at 1.5km), 'Surface treatment of metals' (OR=1.89; 95%CI=1.10-3.28 at 1km), 'Mines' (OR=5.82; 95%CI=1.04-32.43 at 1.5km), 'Explosives/pyrotechnics' (OR=4.04; 95%CI=1.31-12.42 at 4km), and 'Urban waste-water treatment plants' (OR=2.14; 95%CI=1.08-4.27 at 1.5km). CONCLUSIONS: These findings support the need for more detailed exposure assessment of certain substances released by these industries.

Is "fibrodysplasia ossificans progressiva" a vascular disease? A groundbreaking pathogenic model.

Fibrodysplasia ossificans progressiva is the most severe and disabling disorder of ectopic ossification in humans. It is characterized by congenital skeletal abnormalities in association with extraskeletal widespread endochondral osteogenesis. Virtually all patients show the same mutation in the "Activin A type-I/activin-like kinase-2" receptor encoding gene. As a result of this discovery there have been significant advances in the knowledge of the cellular and molecular basis of the disease. Besides allowing a better understanding of ossification process, recent evidence indicates that the primary disturbance lies within basic mechanisms of cell differentiation that are key in several physiological pathways and in the genesis of diseases with a major impact on health. In this article we summarize these breakthroughs, with implications that go beyond the limits of this devastating disease to insinuate a new model of human pathophysiology.

[Implications of the new etiophatogenic approach in the classification of constitutional and genetic bone diseases]. / Implicaciones del nuevo enfoque etiopatogénico en la clasificación de las enfermedades constitucionales y genéticas del hueso.

Recent years have seen an unprecedented increase in the knowledge and understanding of biochemical disturbances involved on constitutional bone disorders. Recognition of the genetic background as the common cause of these diseases prompted the substitution of the term «constitutional¼ by «genetic¼, in referring to them. Understanding physiopathological bases by finding out the altered metabolic pathways as well as their regulatory and control systems, favours an earlier and more accurate diagnosis based on interdisciplinary collaboration. Although clinical and radiological assessment remains crucial in the study of these disorders, ever more often the diagnosis is achieved by molecular and genetic analysis. Elucidation of the damaged underlying molecular mechanisms offers targets potentially useful for therapeutic research in these complex and often disabling diseases.

[Characteristics of Paget's disease in Spain. Data from the National Paget's Register]. / Características de la enfermedad ósea de Paget en España. Datos del Registro Nacional de Paget.

OBJECTIVES: To describe the clinical and epidemiological characteristics of patients included in the National Register of Paget's disease. METHODS: A Register of patients with Paget disease (PD), radiologically confirmed, and pertaining to 25 hospitals was analysed. Clinical and epidemiological data were collected, including age, sex, date and presentations at time of diagnosis, treatment, quality of life (QL) (EuroQol 5D) and perceived health, environmental factors (profession, history of measles, contact with animals, dairy consumption, housing conditions, place of birth and address) and family history (PD history, origin of the ancestors, number of children). We conducted a statistical description of the data. RESULTS: The register included 602 patients with an average age of 62±11 years and a predominance of male (55%). Of the patients included, 79% showed symptoms at the time of diagnosis, mainly pain (83%); 82% had received treatment, mainly bisphosphonates (47% more than one drug). Despite treatment, a significant proportion had limitations in their QL, especially related to pain (64%), mobility (47%) and anxiety/depression (33%). Most of the patients had been exposed to situations which were considered as risk factors. Of the patients included, 14% had family history of PD and 1.5% had children with PD. The ancestors of the familial cases came more frequently from Avila, Salamanca, La Coruña and Malaga. CONCLUSIONS: The pain and the limitation of mobility decrease the QL of patients with PD despite treatment. Frequently, patients have a history of exposure to risk factors.