Familial Mediterranean Fever in Spain: Time Trend and Spatial Distribution of the Hospitalizations.

Familial Mediterranean Fever (FMF) is a rare, hereditary, auto-inflammatory disease. The aims of this study were to explore the time trend and geographical distribution of hospitalizations in Spain from 2008 to 2015. We identified hospitalizations of FMF from the Spanish Minimum Basic Data Set at hospital discharge, using ICD-9-CM code 277.31. Age-specific and age-adjusted hospitalization rates were calculated. The time trend and the average percentage change were analyzed using Joinpoint regression. Standardized morbidity ratios were calculated and mapped by province. A total of 960 FMF-related hospitalizations (52% men) were identified across the period 2008-2015, with an increase in hospitalizations of 4.9% per year being detected (p < 0.05). The risk of hospitalization was higher than expected for the national total (SMR > 1) in 13 provinces (5 in the Mediterranean area), and lower (SMR < 1) in 14 provinces (3 in the Mediterranean area). There was an increase in hospitalizations of patients with FMF in Spain throughout the study period, with a risk of hospitalization that was higher, though not exclusively so, in provinces along the Mediterranean coast. These findings contribute to the visibility of FMF and provide useful information for health planning. Further research should take into account new population-based information, in order to continue monitoring this disease.

The impact of toxic oil syndrome on physical and psychological health status using the HAQ and the PHQ-9 questionnaires.

BACKGROUND: Toxic oil syndrome (TOS) is a multisystemic disease due to a massive intoxication. To evaluate physical and mental health of TOS patients, we used the Health Assessment Questionnaire (HAQ) and the Patient Health Questionnaire-9 (PHQ-9). Additionally, we correlated both questionnaires with the results of the Short Form-36v2 (SF-36v2) Health Survey obtained in the same patients' sample. METHODS: 895 TOS patients who participated in the prior SF-36v2 study were invited to participate. We described patients' demographic and clinical characteristics, HAQ and PHQ-9 results. HAQ and PHQ-9 scores were correlated to the standardised SF-36v2 results obtained in our previous study. RESULTS: In total, 828 (92.5%) TOS annual follow-up and HAQ and 810 (90.5%) PHQ-9 valid questionnaires were analysed. Participants' average age was 65.4 (Standard Deviation (SD): 13.4), 521 (62.9%) were women, 725 (87.6%) reported having at least other chronic disease and 789 (95.3%) an additional TOS-related health problem. Average scores were 0.91 (SD: 0.83) for HAQ, 35.8 (SD: 10.1) for PCS and 37.8 (SD: 11.6) for MCS. Overall, 467 (57.7%) participants had moderate/severe depression (PHQ-9 ≥ 10), but only 229 (49.6%) of them reported having a depression diagnosis. Correlation between questionnaires was very strong for HAQ and physical function SF-36v2 dimension and moderate/fair for the rest of combinations. CONCLUSIONS: TOS cohort presented low/very low health status measured with SF-36v2, moderate difficulties in performing daily activities according to HAQ, and a high prevalence of major depression measured with PHQ-9. High proportion of undiagnosed depression was detected, proving PHQ-9 useful in terms of detecting and promoting depression diagnosis in the cohort.

A population-based study of mortality due to muscular dystrophies across a 36-year period in Spain.

Muscular dystrophies (MD) are a group of rare hereditary degenerative diseases. Our aim was to analyze the mortality pattern in Spain from 1981 to 2016 to assess the temporal trend and discern possible geographic differences using population-based data. Annual deaths related to MD were obtained from the National Statistics Institute with codes 359.1 of the ICD-9 (1981-1998) and G71.0 of the ICD-10 (1999-2016). Age-adjusted mortality rates were calculated and changes in mortality trends were identified. The standardized mortality ratios (SMR) and their respective 95% confidence intervals were calculated by district for 1999-2016. Smoothed SMRs and posterior probability were also assessed and then mapped to look for patterns or geographic distribution. All rates were expressed per 1,000,000 inhabitants. A total of 2,512 deaths (73.8% men) were identified. The age-adjusted mortality rates varied from 0.63 (95% CI 0.40-0.95) in 1981 to 1.51 (95% CI 1.17-1.93) in 2016. MD mortality showed a significant increase of 8.81% per year (95% CI 5.0-12.7) from 1981 to 1990, remaining stable afterwards. Areas with risk of death higher than expected for Spain as a whole were identified, not showing a specific regional pattern. In conclusion, the rising trend in MD mortality might be attributable to advanced improvements in diagnostic techniques leading to a rise in prevalence. Further research on the districts with the highest mortality would be necessary.

Toxic oil syndrome: health-related quality-of-life assessment using the SF-36 Health Survey.

BACKGROUND: Toxic oil syndrome (TOS) is a multisystemic disease due to a massive intoxication that occurred in Spain in 1981 affecting >20 000 persons. This study aims to evaluate the quality of life of the survivors' cohort after 38 years of follow-up using the Short Form 36 (SF-36) Health Survey. METHODS: One thousand patients were selected among the 14 084 alive TOS cohort members in 2018 using a stratified random sampling method. Stratification was performed by the 2017 self-rated health status reported by patients. SF-36 results were compared directly and as standardized (T scores) with the Spanish-population reference values. Relationship between self-rated health status and SF-36 results was assessed. RESULTS: Overall, 900 cohort members participated and 895 valid responses were included in the study. Participants' average age was 65.2 (standard deviation: 13.8) years and 563 (62.9%) participants were women. Participants' distribution by self-rated health status was: 219 (24.5%) good/very good, 415 (46.4%) fair and 261 (29.1%) poor/very poor. Quality of life was below the Spanish-population reference in 84% of the TOS patients (87.2% for women and 78.6% for men) for the Physical Component Summary (PCS) and in 75.4% (81.7% for women and 64.8% for men) for the Mental Component Summary (MCS). PCS and MCS scores decreased similarly for both sexes with worse self-rated health. CONCLUSIONS: Very low quality of life and self-rated health, especially for women, were found in the total TOS participants that can be extrapolated to the TOS survivors' cohort. The TOS cohort still requires standardization of care with integral plans around the country.

Mortalidad atribuida a telangiectasia hemorrágica hereditaria y variabilidad geográfica en España (1981-2016) / Mortality attributed to hereditary haemorrhagic telangiectasia and geographical variability in Spain (1981-2016)

OBJETIVO: Conocer la mortalidad directamente atribuida a la telangiectasia hemorrágica hereditaria (THH) en España, su tendencia temporal y la posible variabilidad geográfica. MÉTODO: El total de los fallecidos por THH de base poblacional se obtuvo del Instituto Nacional de Estadística, seleccionando los códigos 448.0 (CIE 9-MC, 1981-1998) y I78.0 (CIE 10, 1999-2016) como causa básica de defunción. Se calcularon las tasas de mortalidad específicas y ajustadas por edad para cada sexo, las razones de mortalidad estandarizadas (RME) por provincia y comarca, y las RME suavizadas. RESULTADOS: Se identificaron 327 fallecimientos por THH (el 49,5% eran mujeres), siendo la mortalidad más alta a los 80-84 años en los hombres (0,220 por 100.000 habitantes) y a los 75-79 años en las mujeres (0,147 por 100.000 habitantes). No se detectaron cambios temporales entre 1981 y 2016. Las provincias de Navarra, Cantabria, Guipúzcoa, Pontevedra y Las Palmas presentaron un riesgo significativamente superior con respecto a lo esperado para el total nacional, así como las comarcas de Monte Sur (Ciudad Real) y Ripollès (Girona). CONCLUSIONES: Este trabajo ha permitido identificar algunas regiones con mayor riesgo de defunción por THH, si bien se desconoce si estas diferencias se asocian a la distribución de los tipos THH1 y THH2, por lo que son necesarios estudios posteriores para profundizar en las causas de la variabilidad geográfica. Estos hallazgos complementan la información proporcionada por otros estudios y registros, además de ser útiles para la planificación sanitaria

OBJECTIVE: To identify the mortality directly attributed to hereditary haemorrhagic telangiectasia (HHT) in Spain, and to analyze its time trends and geographic variability. METHOD: Population-based deaths due to HHT were selected from the Spanish National Statistics Institute: codes 448.0 (ICD-9, 1981-1998) and I78.0 (ICD-10, 1999-2016) as the basic cause of death. Specific and age-adjusted mortality rates were calculated by sex, as well as standardized mortality ratios (SMR) by province and district, and smoothed SMR. RESULTS: We identified 327 deaths attributed to HHT (49.5% women), with the highest mortality at 80-84 years in men (0.220 per 100,000 inhabitants) and at 75-79 years in women (0.147 per 100,000 inhabitants). Age-adjusted mortality rates did not show any significant time trend between 1981 and 2016 in Spain. The provinces of Navarra, Cantabria, Guipúzcoa, Pontevedra and Las Palmas had higher than expected mortality, as well as the regions of Monte Sur (Ciudad Real) and Ripollès (Girona). CONCLUSIONS: This study has identified some regions with higher risk of death due to HHT in Spain. It is unknown whether these differences are associated with the distribution of types HHT1 and HHT2, and further studies will be necessary to know the determinants of this geographical variability. These findings are useful to complement the information provided by other studies and registries, and for health planning

[Mortality attributed to hereditary haemorrhagic telangiectasia and geographical variability in Spain (1981-2016)]. / Mortalidad atribuida a telangiectasia hemorrágica hereditaria y variabilidad geográfica en España (1981-2016).

OBJECTIVE: To identify the mortality directly attributed to hereditary haemorrhagic telangiectasia (HHT) in Spain, and to analyze its time trends and geographic variability. METHOD: Population-based deaths due to HHT were selected from the Spanish National Statistics Institute: codes 448.0 (ICD-9, 1981-1998) and I78.0 (ICD-10, 1999-2016) as the basic cause of death. Specific and age-adjusted mortality rates were calculated by sex, as well as standardized mortality ratios (SMR) by province and district, and smoothed SMR. RESULTS: We identified 327 deaths attributed to HHT (49.5% women), with the highest mortality at 80-84 years in men (0.220 per 100,000 inhabitants) and at 75-79 years in women (0.147 per 100,000 inhabitants). Age-adjusted mortality rates did not show any significant time trend between 1981 and 2016 in Spain. The provinces of Navarra, Cantabria, Guipúzcoa, Pontevedra and Las Palmas had higher than expected mortality, as well as the regions of Monte Sur (Ciudad Real) and Ripollès (Girona). CONCLUSIONS: This study has identified some regions with higher risk of death due to HHT in Spain. It is unknown whether these differences are associated with the distribution of types HHT1 and HHT2, and further studies will be necessary to know the determinants of this geographical variability. These findings are useful to complement the information provided by other studies and registries, and for health planning.

Tetralogy of Fallot in Spain: a nationwide registry-based mortality study across 36 years.

BACKGROUND: Tetralogy of Fallot (TOF) is the most frequent cyanotic congenital heart defect. TOF mortality has fallen remarkably in recent years due to therapeutic advances. Accordingly, the aim of this study was to assess temporal and spatial variability in TOF-related mortality in Spain across the period 1981-2016, using data drawn from the nationwide population-based registry. METHODS: Annual deaths due to TOF were sourced from the Spanish National Institute of Statistics database by reference to International Classification of Diseases (ICD), 9th and 10th Revision codes, namely, ICD-9 code 745.2 (period 1981-1998) and ICD-10 code Q21.3 (period 1999-2016). Age-specific and age-adjusted mortality rates were calculated, as were standardised mortality ratios (SMRs) by province, district and municipality for the period 1999-2016. RESULTS: A total of 1035 deaths were attributed to TOF (57.78% of them were men and 42.22% were women). The age-adjusted mortality rate ranged from 0.75 per 1,000,000 inhabitants (95% confidence interval [CI]: 0-1.36) in 1981 to 0.03 per 1,000,000 (95% CI: 0.01-0.06) in 2016 for both sexes. In 2011, there was a change in the mortality trend, with a significant decrease of 49.22% per year (p < 0.001). In terms of geographical analysis, some areas with a significantly higher risk of TOF mortality were identified in the south of Spain, though no specific spatial pattern was in evidence. CONCLUSION: The decrease in TOF mortality may be related to improvements in diagnostic and treatment techniques. More studies are needed to analyse regions with a higher mortality risk, in order to improve medical planning and resource allocation, and identify risk factors and preventive measures.

Temporal and Cartographic Analyses of the Distribution within Spain of Mortality Due to Granulomatosis with Polyangiitis (1984⁻2016).

The aim is to conduct a descriptive, population-based study in order to assess temporal and spatial changes in mortality due to granulomatosis with polyangiitis (GPA) in Spain from 1984 to 2016. Mortality data were obtained from the Spanish Annual Death Registry. Deaths in which GPA was the underlying cause were selected using the 446.4 and M31.3 codes from the International Classification of Diseases, 9th and 10th revision. Annual average age at death and age-adjusted mortality rates were calculated. Geographic analysis was performed at municipality and district level. Variations in mortality according to the type of municipality (urban, agro-urban or rural), district and geographic location (degrees of latitude) were assessed using standardized mortality ratios (SMRs) and smoothed-SMRs. Over the whole period, 620 deaths due to GPA were identified. Age at death increased at an average annual rate of 0.78% over the period 1987-2016 (p < 0.05). Age-adjusted mortality rates increased by an annual average of 20.58% from 1984 to 1992, after which they fell by 1.91% a year (p < 0.05). The agro-urban category had the highest percentage (4.57%) of municipalities with a significantly higher GPA mortality rate than expected. Geographic analysis revealed four districts with a higher risk of death due to GPA, two in the North of Spain and two in the South. This population-based study revealed an increase in the age at death attributed to GPA. Age-adjusted mortality rates went up sharply until 1992, after which they started to decline until the end of the study period. Geographic differences in mortality risk were identified but further studies will be necessary to ascertain the reasons for the distribution of GPA disease.

Mortality Due to Cystic Fibrosis over a 36-Year Period in Spain: Time Trends and Geographic Variations.

The aim of this study is to analyze population-based mortality attributed to cystic fibrosis (CF) over 36 years in Spain. CF deaths were obtained from the National Statistics Institute, using codes 277.0 from the International Classification of Diseases (ICD) ninth revision (ICD9-CM) and E84 from the tenth revision (ICD10) to determine the underlying cause of death. We calculated age-specific and age-adjusted mortality rates, and time trends were assessed using joinpoint regression. The geographic analysis by district was performed by standardized mortality ratios (SMRs) and smoothed-SMRs. A total of 1002 deaths due to CF were identified (50.5% women). Age-adjusted mortality rates fell by -0.95% per year between 1981 and 2016. The average age of death from CF increased due to the annual fall in the mortality of under-25s (-3.77% males, -2.37% females) and an increase in over-75s (3.49%). We identified districts with higher than expected death risks in the south (Andalusia), the Mediterranean coast (Murcia, Valencia, Catalonia), the West (Extremadura), and the Canary Islands. In conclusion, in this study we monitored the population-based mortality attributed to CF over a long period and found geographic differences in the risk of dying from this disease. These findings complement the information provided in other studies and registries and will be useful for health planning.

A Nationwide Registry-Based Study on Mortality Due to Rare Congenital Anomalies.

This study aimed to analyse population-based mortality attributed to rare congenital anomalies (CAs) and assess the associated time trends and geographical differences in Spain. Data on CA-related deaths were sourced from annual mortality databases kept by the National Statistics Institute of Spain (1999⁻2013). Based on the ICD-10, only CAs corresponding to rare diseases definition were included in this study. Annual age-adjusted mortality rates were calculated and time trends were evaluated by joinpoint regression analysis. Geographical differences were assessed using standardised mortality ratios and cluster detection. A total of 13,660 rare-CA-related deaths (53.4% males) were identified in the study period. Annual age-adjusted mortality rates decreased by an average of -5.2% (-5.5% males, -4.8% females, p < 0.001). Geographical analysis showed a higher risk of rare-CA-related mortality in regions largely located in the south of the country. Despite their limitations, mortality statistics are essential and useful tools for enhancing knowledge of rare disease epidemiology and, by extension, for designing and targeting public health actions. Monitoring rare-CA-related mortality in Spain has shown a 15-year decline and geographical differences in the risk of death, all of which might well be taken into account by the health authorities in order to ensure equality and equity, and to adopt appropriate preventive measures.

Mortality Statistics and their Contribution to Improving the Knowledge of Rare Diseases Epidemiology: The Example of Hereditary Ataxia in Europe.

Official mortality statistics provide population-based data and serve to improve epidemiological knowledge of rare diseases (RDs), by helping with the description of the natural history of the disease. They are an important complement of registries and estimates of disease burden and costs. At the same time, they heighten both the visibility of these diseases and the interest in their study and the search for treatments that may increase survival. This chapter contains a European analysis of hereditary ataxia mortality, which considers the time trend in different countries and the geographical variability in risk of death. Despite the limitations of applying this data source to RDs, mortality statistics share criteria which facilitate international comparisons and are of great utility for obtaining sufficiently uniform and robust time series for analysis of low-prevalence diseases.

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.

The Quality of Rare Disease Registries: Evaluation and Characterization.

BACKGROUND: The focus on the quality of the procedures for data collection, storing, and analysis in the definition and implementation of a rare disease registry (RDR) is the basis for developing a valid and long-term sustainable tool. The aim of this study was to provide useful information for characterizing a quality profile for RDRs using an analytical approach applied to RDRs participating in the European Platform for Rare Disease Registries 2011-2014 (EPIRARE) survey. METHODS: An indicator of quality was defined by choosing a small set of quality-related variables derived from the survey. The random forest method was used to identify the variables best defining a quality profile for RDRs. Fisher's exact test was employed to assess the association with the indicator of quality, and the Cochran-Armitage test was used to check the presence of a linear trend along different levels of quality. RESULTS: The set of variables found to characterize high-quality RDRs focused on ethical and legal issues, governance, communication of activities and results, established procedures to regulate access to data and security, and established plans to ensure long-term sustainability. CONCLUSIONS: The quality of RDRs is usually associated with a good oversight and governance mechanism and with durable funding. The results suggest that RDRs would benefit from support in management, information technology, epidemiology, and statistics.

Comparative cost-effectiveness analysis of oral triptan therapy for migraine in four European countries.

AIM: To assess the differences in the cost-effectiveness of oral triptan therapy for migraines among European countries. METHODS: A cost-effectiveness analysis of triptan therapy for migraine was conducted from a health-care payer perspective in four European countries (France, Italy, Spain and the UK). The study included those orally administered triptans available in all of these countries (almotriptan, brand-name sumatriptan, generic sumatriptan, zolmitriptan), and it was performed using a decision-tree model that incorporated costs of the drugs and probabilities associated with the possible events and outcomes. Average cost-effectiveness ratios were calculated in two different scenarios. RESULTS: The average cost-effectiveness ratio showed wide variations across the different countries, these differences being up to 131 % (almotriptan), 77 % (brand-name sumatriptan), 153 % (generic sumatriptan) and 77 % (zolmitriptan). Generic sumatriptan was the most cost-effective drug analysed in the studied countries. CONCLUSIONS: Caution must be taken when trying to transfer conclusions of pharmacoeconomics studies on migraines even in neighbouring countries. This cross-country variability is a concern for decision-makers and also for the elaboration of international recommendations and clinical practice guidelines.

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.

Cost-effectiveness analysis of burning mouth syndrome therapy.

OBJECTIVE: To study the cost-effectiveness of four alternative treatments for burning mouth syndrome (BMS). METHODS: A cost-effectiveness analysis was conducted from a healthcare payer perspective of four therapy strategies (amisulpride, paroxetine, sertraline and topical clonazepam), using a decision-tree model that incorporated direct healthcare costs and probabilities associated with the possible events and outcomes. Average cost-effectiveness and incremental cost-effectiveness ratios were calculated. Sensitivity analyses included the costs of brand name and generic drugs in five European countries (France, Italy, the Netherlands, Spain and UK), as well as two scenarios with different treatment length. RESULTS: Of the drugs analysed, topical clonazepam proved to be the most cost-effective therapy. Although generic proved more efficient than brand name drugs, they displayed no advantage over brand name topical clonazepam. The Netherlands was the country with the highest overall drug efficiency. Sensitivity analyses highlighted the robustness of the model, because topical clonazepam proved to be the most efficient therapy under all the different scenarios. CONCLUSIONS: Topical clonazepam, which previous analyses of clinical evidence have shown to be the drug of choice for BMS, also proved to be the most cost-effective of the drugs analysed for this condition.

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

El avance en el conocimiento de las alteraciones bioquímicas que causan las enfermedades constitucionales óseas no tiene precedentes. La constatación de que su característica esencial es el trasfondo genético común a todas ellas ha dado lugar a una propuesta de alcance: sustituir el término «constitucionales» por «genéticas» para referirse a estas entidades. La comprensión de los mecanismos fisiopatológicos implicados, identificando el punto exacto de la vía metabólica alterada y sus sistemas de regulación y control, facilita realizar un diagnóstico preciso, basado en la colaboración interdisciplinar, en un tiempo muy inferior del que requería el enfoque tradicional. Además, aunque la correcta valoración de las manifestaciones clínicas y radiológicas sigue siendo crucial, el diagnóstico de certeza se basa cada vez con mayor frecuencia en la aplicación de las nuevas técnicas de análisis genético y molecular. Por último, el esclarecimiento de las complejas alteraciones subyacentes a estos trastornos descubre unas dianas moleculares de gran utilidad potencial en la investigación terapéutica de unas enfermedades que a menudo limitan de manera notable la calidad de vida y que, casi sin excepciones, todavía carecen de un tratamiento eficaz (AU)

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 «constitutional» by «genetic», 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 (AU)

[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.