Análisis de la microarquitectura ósea mediante tomografía computada periférica de alta resolución en pacientes con enfermedad celíaca al diagnóstico y un año después del comienzo de la dieta libre de gluten

La enfermedad celíaca (EC) es una enteropatía autoinmune que afecta el 1% de la población. Entre las manifestaciones extraintestinales, está bien establecido que el deterioro de la masa ósea condicion aun mayor riesgo de fracturas óseas, que es revertido por el tratamiento con dieta libre de gluten (DLG). Los avances de la tecnología condujeron a la introducción de la tomografía computada cuantitativa periférica de alta resolución (HR-pQCT), que permite la evaluación in vivo de la microarquitectura del hueso y la densidad ósea volumétrica. Hasta el momento actual no existen estudios que evalúen la microarquitectura ósea de los huesos periféricos de pacientes con EC. El objetivo del proyecto fue establecer los cambios en la microarquitectura ósea trabecular y cortical de huesos periféricos (radio y tibia distales) mediante la HR-pQCT al momento del diagnóstico de EC (estudio transversal), y las modificaciones producidas luego de un año de DLG (estudiolongitudinal) en pacientes femeninas consecutivas premenopáusicas con diagnóstico recientede EC. Como grupo de control se consideró un número similar de mujeres sanas de la misma edad. Como resultado, el estudio transversal demostró que, comparados con la población control sana, los pacientes con reciente diagnóstico de enfermedad celíaca tienen parámetros de deterioro significativo de la microestructura de huesos periféricos: densidad volumétrica total, número y espesor de trabéculas, y la densidad cortical, tanto en el radio distal como la tibia. Publicado (Bone 2015;76: 149-57). El estudio longitudinal, al año del momento del diagnóstico e iniciada la DLG, demostró que la terapéutica genera un incremento significativo de los parámetros corticales deteriorados en condiciones basales (la densidad volumétrica total y el espesor de las trabéculas). Dicha mejoría no se demostró en el compartimiento óseo cortical. Es muy posible que la mejoría a dicho nivel requiera un análisis luego del tratamiento más prolongado. Por estos motivos, el estudio continúa analizando la evolución ósea en el largo plazo (en publicación en J Bone Min Research). El estudio transversal original permitió conocer, por primera vez, el factor íntimo responsable del deterioro de la estructura ósea de pacientes con EC, que es determinante del elevado riesgo de fracturas que presentan los pacientes antes del diagnóstico. El estudio longitudinal permite conocer,por primera vez, las razones por las cuales dicho riesgo elevado desaparece con la implementaciónde una DLG.Celiac disease (CD) is a systemic autoimmune enteropathy affecting 1% of the general population. Among extra-intestinal manifestations, the impairment of bone mass which may result in bone fractures is relevant. Such affectation may be reverted by treatment with a gluten-free diet (GFD).The high-resolution peripheral quantitative computed tomography (HR-pQCT) has allowed the in vivo analysis of the bone microarchitecture and the bone volumetric density. The technique allows a differential measurement of trabecular and cortical bone compartments and has been called the virtual bone biopsy due to the very high resolution (82μm). Up to now, no studies explored microarchitecture of peripheral bones of patients with CD. Also, there is no insight about the effect of the GFD diet in bone micro structural damage.The aim of the project was to determine changes in bone micro-structure both of the trabecular and cortical of peripheral bones (distal radio and tibia) estimates by HR-pQCT at the time of diagnosis (cross-sectional study) and, to assess changes induced by the GFD after one-year of starting treatment (longitudinal study) in premenopausal consecutive female patients with newly diagnosed EC. As a control group a similar number of healthy women of the same age was considered. As a result, the cross-sectional study showed that, compared with healthy population controls, patients with newly diagnosed celiac disease have parameters significant deterioration of the microstructure of peripheral bones: total number and thickness of trabeculae bulk density, and cortical density at both the distal radius and the tibia. Published (Bone 2015; 76: 149-57). The longitudinal study, one year after the time of diagnosis and initiation of DLG, demonstrated that therapeutic generates a significant increase in cortical impaired at baseline parameters (volume density and total thickness of the trabeculae). This improvement was not demonstrated in cortical bone compartment. It is quite possible that the improvement at this level requires an analysis after longer treatment. For these reasons the study continues to analyze bone development in the longterm (in publication in J Bone Min Research).The original cross-sectional study allowed to know, for the first time, the intimate factor responsible for the deterioration of the bone structure of patients with CD which is determinative of the increased risk of fracture patients present before diagnosis. The longitudinal study provides insight for the first time, the reasons for this increased risk disappears with the implementation of a DLG

Hipopara-Red, Real Life Experience in 322 Patients with Hypoparathyroidism

Context:Hypoparathyroidism is a rare disease and as such, its natural history, long term complications and correct clinical management remain unclear.ObjectiveTo describe the natural history and clinical characteristics of the disease.Design and settingTopresent a retrospective observational analysis from seven specialized centers in Buenos Aires, Argentina.Patientschronic hypoparathyroid patients followed up between 1985 and December 2018.Main Outcome Measuresdata on demographics, etiology, clinical complications, biochemical parameters, DXA values and treatment doses were collected.Results322 subjects with chronic hypoparathyroidism were included, 85.7 % were female. Mean age was 55.2 ± 16.8 years and mean age at diagnosis was 43.8 ± 16.8. Prevalence of surgical hypoparathyroidism was 90.7 %, most common causes being thyroid carcinoma and benign thyroid disease. A history of hypocalcemia requiring hospitalization was present in 25.7 % and 4.3 % had a history of seizures. Overall, 40.9 % had reported at least one neuromuscular symptom. Renal insufficiency was present in 22.4 % and was significantly associated with age (p<0.0001). Hyperphosphatemia was present in 42 %. A history of severe hypocalcemia, paresthesias, tetany, ganglia calcifications, seizures and cataracts was significantly higher in nonsurgical patients.ConclusionAlthough these patients were followed up by experienced physicians, clinical management was heterogeneous and probably insufficient to assess all the potential complications of this chronic disease. Almost 70 % of this group of patients met the experts´ indications for considering the use of rhPTH 1-84. Being aware of this fact is the first step to improve our medical management of this disease in the future.Fil: Zanchetta, María Belén. Universidad del Salvador; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Robbiani, Damián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Universidad del Salvador; ArgentinaFil: Oliveri, María Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Giacoia, Evangelina. Hospital Nacional Profesor Alejandro Posadas; ArgentinaFil: Frigeri, Adriana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Dr. Teodoro Álvarez"; ArgentinaFil: Kallsbrum, Silvia. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Carlos Durand; ArgentinaFil: Salerni, Helena. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Carlos Durand; ArgentinaFil: Lucas, Sabrina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. División Osteopatías; ArgentinaFil: Diaz, Adriana. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. División Osteopatías; ArgentinaFil: Perez, Betiana. Hospital Italiano; ArgentinaFil: Pieroni, Luisina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Dr. Teodoro Álvarez"; ArgentinaFil: Arce Lange, María Auxiliadora. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Dr. Teodoro Álvarez"; ArgentinaFil: Tormo, Silvina. Hospital Nacional Profesor Alejandro Posadas.; ArgentinaFil: Kitaigrodsky, Ariela. Hospital Italiano; ArgentinaFil: Galich, Ana María. Hospital Italiano; Argentin

Las mujeres postmenopáusicas con sarcopenia tienen mayor prevalencia de caídas y fracturas vertebrales

Recently, a new consensus of the European Working Group on Sarcopenia in Older People (EWSOP2) recommended new cut-off points for the diagnosis of sarcopenia. The aim of the present manuscript was to assess the prevalence of sarcopenia in postmenopausal women and its relationship with bone mineral density, falls and fragility fractures according to EWGSOP2. In this cross-sectional study, 250 ambulatory postmenopausal women over 60 years of age were included. Lumbar spine and hip bone mineral density (BMD) and whole-body composition were assessed by dual-energy X-ray absorptiometry (DXA). Muscle strength was evaluated by handgrip dynamometry and physical performance by a 4-m walk gait speed and five-repetition sit-to-stand test. Sarcopenia was defined according to EWGSOP2 as low muscle strength (handgrip) and low muscle mass (appendicular skeletal muscle mass index by DXA). A sarcopenia prevalence of 4% was found in the whole group increasing with age being 12.5% in ≥ 80- year-old. A higher percentage of falls, prevalence of osteoporosis and vertebral fractures were found in the sarcopenic group. Sarcopenia increased 6.0-fold the likelihood of having a fragility fracture. Women with sarcopenia had significantly lower femoral neck BMD and higher frequency of falls and vertebral fractures. According to our results, identifying patients with sarcopenia might be a useful tool to detect adults at higher risk of falls and fractures.Recientemente el grupo de trabajo europeo sobre sarcopenia en adultos mayores (EWGSOP2) recomendó nuevos criterios y valores de referencia para el diagnóstico de sarcopenia. El objetivo del presente trabajo fue evaluar la prevalencia de sarcopenia en mujeres postmenopáusicas en nuestro medio y su relación con densidad mineral ósea, caídas y fracturas por fragilidad. Este es un estudio de diseño transversal en el cual se incluyeron un total de 250 mujeres ambulatorias mayores de 60 años. La densidad mineral ósea (DMO) de columna lumbar y cadera y la composición corporal fueron evaluados por absorciometría dual de rayos X (DXA). La fuerza fue evaluada por dinamometría de puño; para el rendimiento físico se utilizó caminata de 4 m y la prueba de levantarse y sentarse de una silla (5 repeticiones). La sarcopenia se definió de acuerdo a EWGSOP2 como baja fuerza muscular (dinamometría) y baja masa muscular (índice de masa muscular esquelética por DXA). El 4% de las mujeres cumplía con los criterios de sarcopenia siendo aún mayor en aquellas ≥ 80 años. Las mujeres con sarcopenia presentaron significativamente mayor frecuencia de caídas, osteoporosis y fracturas vertebrales. El riesgo de fracturas por fragilidad se vio incrementado 6 veces en las mujeres con sarcopenia. El diagnóstico de sarcopenia podría considerarse una herramienta útil para identificar a aquellos adultos con riesgo incrementado de caídas y fracturas.Fil: Zanchetta, María Belén. Instituto de Diagnóstico e Investigaciones Metabólicas; Argentina. Universidad del Salvador; ArgentinaFil: Abdala, Rubén. Instituto de Diagnóstico e Investigaciones Metabólicas; Argentina. Universidad del Salvador; ArgentinaFil: Massari, Fabio. Instituto de Diagnóstico e Investigaciones Metabólicas; Argentina. Universidad del Salvador; ArgentinaFil: Rey, Paula. Instituto de Diagnóstico e Investigaciones Metabólicas; Argentina. Universidad del Salvador; ArgentinaFil: Spivacow, Rodolfo. Instituto de Diagnóstico e Investigaciones Metabólicas; ArgentinaFil: Miechi, Lara. Instituto de Diagnóstico e Investigaciones Metabólicas; ArgentinaFil: Longobardi, Vanesa. Instituto de Diagnóstico e Investigaciones Metabólicas; Argentina. Universidad del Salvador; ArgentinaFil: Brun, Lucas Ricardo Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; Argentin

Diagnosis and Management of Tumor-Induced Osteomalacia: Perspectives from Clinical Experience

PurposeTumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome of abnormal phosphate and vitamin D metabolism caused by typically small endocrine tumors that secrete fibroblast growth factor 23 (FGF23). TIO is characterized clinically by progressive musculoskeletal pain, fatigue, proximal muscle weakness, and multiple fractures, leading to long-term disability. Misdiagnosis and delayed diagnosis are common because of the nonspecific symptoms, and several years may elapse before patients receive an accurate diagnosis and appropriate treatment. Thus, it is vital that awareness of the appropriate recognition and management of TIO is increased among healthcare professionals who may encounter patients with suspected TIO.MethodsA roundtable meeting was held on 10 January 2020 in Dallas, TX, USA, to gather perspectives on the diagnosis and treatment of TIO. The following topics were considered: clinical presentation, patient history, differential diagnosis, laboratory assessment, imaging, venous sampling, and treatment.ResultsThis report provides a summary of our collective experiences in the management of TIO.Main conclusionsLaboratory tests are mandatory to expedite TIO diagnosis and should include measurement of fasting serum phosphorus, renal phosphate reabsorption, serum 1,25-dihydroxyvitamin D, and serum FGF23 levels. Functional and anatomical imaging are essential to locate the FGF23-secreting tumor(s) causing TIO. Surgical resection is often a curative treatment when the tumor can be localized; however, better management of patients who cannot be operated on with targeted therapies is needed. Further efforts to increase awareness of TIO within the medical community, and education on recommended diagnostic and treatment pathways are required to improve the management of this debilitating disease

Effect of Teriparatide on Bone Mineral Density and Bone Markers in Real-Life: Argentine Experience

Purpose. To evaluate the effect of teriparatide (TPTD) on bone mineral density (BMD) and bone markers under clinical practice conditions. To assess whether the results in real-life match those published in clinical trials. Methods. Cross-sectional study of postmenopausal women treated with TPTD for at least 12 months. Results. 264 patients were included in the study. Main characteristics are as follows: age: 68.7 ± 10.2 years, previous fractures: 57.6%, and previously treated with antiresorptive (AR-prior): 79%. All bone turnover markers studied significantly increased after 6 months. CTX and BGP remained high up to 24 months, but total and bone alkaline phosphatase returned to basal values at month 18. There was a significant increase in lumbar spine (LS) BMD after 6 months (+6.2%), with a maximum peak at 24 months (+13%). Femoral neck (FN) and total hip (TH) BMD showed a significant increase later than LS (just at month 12), reaching a maximum peak at month 24 (FN + 7.9% and TH + 5.5%). A significant increase in LS BMD was found from month 6 to month 24 compared to basal in both AR-naïve, and AR-prior patients (+16.7% and +10.5%, respectively), without significant differences between the two groups. Comparable results were found in FN and TH BMD. Main conclusions. As reported in real-life clinical studies, treatment of osteoporotic postmenopausal women with TPTD induced a significant increase in bone turnover markers from month 6 onward and an increase in BMD from months 6–12 with continuous gain up to month 24. The real-life results of our study matched the results of randomized clinical trials. In addition, TPTD induced an increase in BMD, regardless of the previous use of AR

Interdisciplinary management of FGF23-related phosphate wasting syndromes: a Consensus Statement on the evaluation, diagnosis and care of patients with X-linked hypophosphataemia

X-linked hypophosphataemia (XLH) is the most frequent cause of hypophosphataemia-associated rickets of genetic origin and is associated with high levels of the phosphaturic hormone fibroblast growth factor 23 (FGF23). In addition to rickets and osteomalacia, patients with XLH have a heavy disease burden with enthesopathies, osteoarthritis, pseudofractures and dental complications, all of which contribute to reduced quality of life. This Consensus Statement presents the outcomes of a working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, and provides robust clinical evidence on management in XLH, with an emphasis on patients' experiences and needs. During growth, conventional treatment with phosphate supplements and active vitamin D metabolites (such as calcitriol) improves growth, ameliorates leg deformities and dental manifestations, and reduces pain. The continuation of conventional treatment in symptom-free adults is still debated. A novel therapeutic approach is the monoclonal anti-FGF23 antibody burosumab. Although promising, further studies are required to clarify its long-term efficacy, particularly in adults. Given the diversity of symptoms and complications, an interdisciplinary approach to management is of paramount importance. The focus of treatment should be not only on the physical manifestations and challenges associated with XLH and other FGF23-mediated hypophosphataemia syndromes, but also on the major psychological and social impact of the disease

Consenso de expertos colombianos sobre recomendaciones basadas en evidencia para el diagnóstico, tratamiento y seguimiento del raquitismo hipofosfatémico ligado al cromosoma X (RHLX)

Background: X-linked hypophosphatemic rickets is a hereditary disease that generates alterations in bone mineral homeostasis. The morbidity of the condition has been variable in previous decades and even contradictory, probably due to the definition of the case and the diagnostic confirmation. Our propose was to generate evidence-informed recommendations for the diagnosis, treatment, and follow-up of patients with suspected or diagnosed XLHR. Results: After the screening and selection process for 1041 documents, 38 were included to answer the questions raised by the developer group. 97 recommendations about the diagnosis, treatment, and follow-up of patients with suspected or diagnosed XLHR were approved by the experts consulted through modified Delphi consensus. The quality of the evidence was low. Conclusions: The recommendations proposed here will allow early and timely diagnosis of X-linked hypophosphatemic rickets, while optimizing resources for its treatment and follow-up and help clarify the burden of disease and improve health outcomes for this population