Threshold based on bone mineral density for therapeutic decision-making in postmenopausal women and men over 50 years old under glucocorticoid therapy.

INTRODUCTION AND AIM: T-score bone mineral density (BMD) thresholds may influence guidance for treatment in patients under glucocorticoid (GC) therapy. Different BMD thresholds have been described but there is no international consensus. The aim of this study was to find a threshold to help in treatment decision-making in the population under GC therapy. METHODS: A working group representing three scientific societies from Argentina was convened. The first team was formed by specialists with expertise in glucocorticoid-induced osteoporosis (GIO) who voted according to summary of evidence. The second team was constituted by a methodology group who coordinated and supervised each stage. We conducted two systematic reviews to synthesize the evidence. The first included trials of drugs used in GIO to analyze the BMD cut-off used as inclusion criteria. In the second, we analyzed the evidence regarding the densitometric thresholds to discriminate between fractured and non-fractured patients under GC treatment. RESULTS: In the first review, 31 articles were included for qualitative synthesis and more than 90% of the trials included patients regardless of their densitometric T-score or range of osteopenia. In the second review, 4 articles were included and more than 80% of the T-scores were in the range -1.6 to -2.0. The summary of findings was analyzed and put to a vote. CONCLUSIONS: With more than 80% agreement of the voting expert panel, a T-score≤-1.7 was considered the most appropriate for treatment in postmenopausal women and men over 50 years of age under GC therapy. This study could help in treatment decision-making in patients under GC therapy without fractures but other fracture risk factors should certainly be considered.

Threshold based on bone mineral density for therapeutic decision-making in postmenopausal women and men over 50 years old under glucocorticoid therapy / Umbral densitométrico de densidad mineral ósea para considerar tratamiento en pacientes mujeres posmenopáusicas y hombres mayores de 50 años en tratamiento con glucocorticoids

Introduction and aim: T-score bone mineral density (BMD) thresholds may influence guidance for treatment in patients under glucocorticoid (GC) therapy. Different BMD thresholds have been described but there is no international consensus. The aim of this study was to find a threshold to help in treatment decision-making in the population under GC therapy. Methods: A working group representing three scientific societies from Argentina was convened. The first team was formed by specialists with expertise in glucocorticoid-induced osteoporosis (GIO) who voted according to summary of evidence. The second team was constituted by a methodology group who coordinated and supervised each stage. We conducted two systematic reviews to synthesize the evidence. The first included trials of drugs used in GIO to analyze the BMD cut-off used as inclusion criteria. In the second, we analyzed the evidence regarding the densitometric thresholds to discriminate between fractured and non-fractured patients under GC treatment. Results: In the first review, 31 articles were included for qualitative synthesis and more than 90% of the trials included patients regardless of their densitometric T-score or range of osteopenia. In the second review, 4 articles were included and more than 80% of the T-scores were in the range −1.6 to −2.0. The summary of findings was analyzed and put to a vote. Conclusions: With more than 80% agreement of the voting expert panel, a T-score≤−1.7 was considered the most appropriate for treatment in postmenopausal women and men over 50 years of age under GC therapy. This study could help in treatment decision-making in patients under GC therapy without fractures but other fracture risk factors should certainly be considered.(AU)

Introducción y objetivo: Los umbrales del T-score de densidad mineral ósea (DMO) podrían influir en el tratamiento de pacientes bajo terapia con glucocorticoides (GC). Se han descrito diferentes umbrales, pero no existe un consenso internacional. El objetivo de este trabajo fue encontrar un umbral que ayude en la decisión terapéutica en la población bajo tratamiento con GC. Métodos: Se convocó un grupo de trabajo en representación de tres sociedades científicas de Argentina. El primer equipo estuvo formado por especialistas con experiencia en osteoporosis inducida por glucocorticoides (OIG), quienes estuvieron a cargo de la votación basada en la evidencia. El segundo equipo estuvo a cargo de la metodología coordinando y supervisando cada etapa. Realizamos dos revisiones sistemáticas: la primera incluyó ensayos de fármacos utilizados en OIG para analizar el T-score considerado como criterio de inclusión. En la segunda, analizamos la evidencia sobre umbrales densitométricos para la discriminación de pacientes fracturados y no fracturados bajo tratamiento con GC. Resultados: En la primera revisión se incluyeron 31 artículos donde se halló que más de 90% de los ensayos incluyeron pacientes independientemente del T-score o en el rango de osteopenia. En la segunda revisión se incluyeron cuatro artículos donde observamos que más de 80% de los valores de T-score se encontraban entre -1,6 y -2,0. Conclusiones: Con un acuerdo superior a 80% del panel de expertos, un T-score ≤ -1,7 se consideró el más adecuado para el tratamiento en mujeres posmenopáusicas y hombres mayores de 50 años bajo tratamiento con GC. Este estudio podría ayudar en la decisión terapéutica en pacientes bajo tratamiento con GC sin fracturas, pero ciertamente deberían considerarse otros factores de riesgos de fracturas complementarios.(AU)

Normocalcemic primary hyperparathyroidism: 99mTc SestaMibi SPECT/CT results compare with hypercalcemic hyperparathyroidism.

CONTEXT: Normocalcemic primary hyperparathyroidism (nPHPT) is defined by an inappropriately increased serum PTH with normal serum calcium. Information about the diagnostic yield of parathyroid SPECT/CT scan and ultrasonography in nHPPT is limited and not conclusive. PURPOSE: To evaluate the positivity rate of 99m Tc-Sestamibi SPECT/CT scan in nPHTP compared with classical hypercalcemic PHPT (cPHPT). MATERIALS AND METHODS: We retrospectively studied 125 patients with 99m Tc-Sestamibi SPECT/CT scans. Subjects were divided into 2 groups: cPHPT (n = 93) and nPHPT (n = 32). RESULTS: The detection rate of 99m Tc-Sestamibi SPECT/CT in cPHPT was 86,02% (80/93) and 59.37%, in nPHPT (19/32), p = .003. No significant differences were seen between the SPECT/CT scan and ultrasonography (p = .28) and the agreement was higher in cPHPT than in nPHPT, p = .03. Sensitivity of 99m Tc-Sestamibi-SPECT/CT was 98% on a per-patient basis (PPV 96%) and 91% on a per-lesion basis (PPV 88%). Glandular size was smaller in nPHPT (mean value 6.8 mm) and it was related only with PTH value. CONCLUSION: Localization rate of parathyroid hyperfunctioning tissue with 99m Tc-Sestamibi SPECT/CT is lower in nPHPT and it is related to a smaller glandular size. However, our study suggests that the positivity rate and sensitivity are nonnegligible by adding SPECT/CT. The reduction in the detection rate in nPHPT could benefit techniques with higher resolution such as 18 F-Choline PET/CT when the clinical context justifies it.

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. OBJECTIVE: To describe the natural history and clinical characteristics of the disease. DESIGN AND SETTING: To present a retrospective observational analysis from 7 specialized centers in Buenos Aires, Argentina. PATIENTS: Chronic hypoparathyroid patients followed-up between 1985 and December 2018. MAIN OUTCOME MEASURES: Data on demographics, etiology, clinical complications, biochemical parameters, dual-energy x-ray absorptiometry (DXA) values, and treatment doses were collected. RESULTS: A total of 322 subjects with chronic hypoparathyroidism were included; 85.7% were female, the mean age was 55.2 ±â€…16.8 years, and the mean age at diagnosis was 43.8 ±â€…16.8 years. Prevalence of surgical hypoparathyroidism was 90.7%, with the most common causes being thyroid carcinoma and benign thyroid disease. A history of hypocalcemia requiring hospitalization was present in 25.7% of the whole group and in 4.3% of patients who had a history of seizures. Overall, 40.9% of our patients had reported at least 1 neuromuscular symptom. Renal insufficiency was present in 22.4% of our patients and was significantly associated with age (P < 0.0001). Hyperphosphatemia was present in 42% of patients. A history of severe hypocalcemia, paresthesias, tetany, ganglia calcifications, seizures, and cataracts was significantly higher in nonsurgical patients. CONCLUSION: Although 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 the study's group of patients met the experts' indications for considering the use of rhPTH 1-84. Being aware of this fact is the 1st step in improving our medical management of this disease in the future.

Usefulness of 18F-Fluorocholine Positron Emission Tomography-Computed Tomography in Locating Lesions in Hyperparathyroidism: A Systematic Review.

IMPORTANCE: Identifying parathyroid glands correctly before a surgical procedure is essential to perform minimally invasive surgery. First-line tests with discordant or negative results underscore the need for more accurate imaging tests, thus decreasing the requirement for bilateral neck exploration or reintervention. OBJECTIVE: To review the available evidence to determine positive predictive value, negative predictive value, sensitivity, and specificity in clinical cases in which 18F-fluorocholine positron emission tomography-computed tomography (PET/CT) could be useful as a method to locate the lesions, and the benefits and controversial aspects of the method. EVIDENCE REVIEW: A search was conducted using the PubMed Central and Cochrane Library databases for studies published in English from July 26, 2014, to November 30, 2018, using the search terms 18 choline, 18F choline, 18F-choline, 18 fluorocholine PET CT, hyperparathyroidism, primary hyperparathyroidism, secondary hyperparathyroidism, tertiary hyperparathyroidism, persistent hyperparathyroidism, recurrent hyperparathyroidism, ectopic hyperparathyroidism, and parathyroid adenoma. Other inclusion criteria were reporting at least 1 of the following measurements: negative or positive predictive value, sensitivity, and specificity of 18F-fluorocholine PET/CT in the diagnosis of hyperparathyroidism (HPT). Exclusion criteria were language other than English, use of a tracer other than 18F-fluorocholine, reports of a single case, and studies not related to HPT. The Oxford Centre classifications for levels of evidence were used. FINDINGS: Sixteen studies fulfilled the inclusion criteria, comprising a total of 619 patients. Selected studies included 10 prospective cohort studies, 5 retrospective cohort studies, and 1 case series. Of the subtypes of HPT diagnosed using 18F-fluorocholine PET/CT, 579 were primary HPT, 22 were secondary HPT, 1 was tertiary HPT, and 7 were associated with multiple endocrine neoplasia type I. Pathologically, the neoplasms comprised 459 adenomas, 59 hyperplasia, and 19 double adenomas. CONCLUSIONS AND RELEVANCE: 18F-fluorcholine PET/CT may be indicated when results of first-line tests are negative or discordant and in challenging clinical situations where locating the source of HPT is difficult.

Utilidad de la 18f-colina pet/tc en hiperparatiroidismo primario persistente o recurrente: experiencia inicial / Usefulness of 18f-choline pet / tc in persistent or recurrent primary hyperparathyroidism: initial experience

El hiperparatiroidismo persistente/recurrente representa un desafío en la localización del tejido paratiroideo hiperfuncionante. En esta subpoblación, los métodos convencionales ofrecen un menor rédito diagnóstico. La 18F-colina PET/TC podría ser una buena alternativa dada su mejor resolución espacial, capacidad de detectar glándulas ectópicas y la conjunción de la imagen molecular y anatómica. Sin embargo, la evidencia en este subgrupo de pacientes es escasa. Objetivo: evaluar la utilidad de la 18F-colina PET/TC como método de localización en el hiperparatiroidismo persistente o recurrente. Materiales y métodos: se analizaron los pacientes con 18F-colina PET/TC para hiperparatiroidismo entre diciembre de 2015 y enero de 2018 en un centro terciario de alto volumen. Se analizaron el número de lesiones, su localización, tamaño y el Standard Uptake Value máximo (SUV max) en las imágenes tempranas y tardías. Se compararon los resultados con los métodos convencionales. Resultados: 7 de 15 pacientes habían sido operados previamente (persistentes/recurrentes). La 18F-colina PET/TC detectó 6/7 casos (83,33%), la ecografía cervical 1/4 (25%) y el SPECT de paratiroides y la resonancia nuclear magnética 2/5 (40%). El SUV max obtenido fue variable, en la mitad de los casos a los 10 minutos y en los restantes a la hora; el tamaño promedio de las lesiones fue 8,61 mm (6-12 mm). Conclusiones: la 18F-colina PET/TC muestra una alta tasa de detección en los pacientes con hiperparatiroidismo persistente/recurrente. La combinación del comportamiento biológico del PET con los hallazgos morfológicos aportados por la TC con contraste endovenoso le ofrecería ventajas sobre otros estudios que podrían posicionarlo como método de primera línea en esta subpoblación. (AU)

Persistent or recurrent hyperparathyroidism represents a challenge regarding the localization of the hyper-functioning parathyroid tissue. In this subpopulation of hyperpharathyroid patients, conventional methods have a low diagnostic yield. The 18F-choline PET /CT could be a good alternative given its better spatial resolution, ability to detect ectopic glands, and the conjunction of the molecular and anatomical image. However, the evidence in this subgroup of patients is limited. Objective: to evaluate the utility of 18F-choline PET/ CT as a localization method in persistent or recurrent hyperparathyroidism. Materials and methods: patients with 18F-choline PET / CT for hyperparathyroidism between December 2015 and January 2018 in a high-volume tertiary center were included. The number of lesions, and their location, size, and maximum Standard Uptake Value (SUV) in the early and late images were analyzed. The results were compared to conventional methods. Results: 7 of 15 patients had been previously operated (persistent/recurrent). 18F-choline PET / CT detected 6/7 cases (83,33%), cervical ultrasound 1/4 (25%) and parathyroid SPECT and magnetic resonance 2/5 (40%). The maximum SUV was variable, one half at 10 minutes and the other half at 60 minutes; the average size of the lesions was 8.61 mm (6-12 mm). Conclusions: 18F-Choline PET / CT shows a high detection rate in patients with persistent / recurrent hyperparathyroidism. The combination of the biological behavior of PET with the morphological findings provided by CT with intravenous contrast would offer advantages over other studies that could position it as a first line method in this subpopulation. (AU)

Fracturas vertebrales múltiples postsuspensión de denosumab: revisión del tema a partir de dos casos clínicos / Discontinuation of denosumab and multiple vertebral fractures: report of two cases and review of the literature

Los tratamientos para osteoporosis se indican por tiempo variable dependiendo del tipo de droga, anabólica o anticatabólica, y de la gravedad de la enfermedad. Denosumab es un anticuerpo monoclonal totalmente humano que inhibe a RANK-L evitando de esa manera la interacción entre RANKL-RANK, con la consiguiente inhibición de la formación de los osteoclastos, su activación y sobrevida. Disminuye la resorción ósea cortical y trabecular. Su administración subcutánea de 60 mg cada 6 meses al cabo de 3 años ha demostrado reducción de la resorción ósea, incremento de la densidad mineral ósea y disminución de las fracturas vertebrales, no vertebrales y de cadera. Está indicado para el tratamiento de la osteoporosis con alto riesgo de fractura. Su mecanismo de acción es reversible. Se han descripto pérdida de la DMO y elevación de los marcadores de remodelado óseo postsuspensión. Una situación clínica grave son las fracturas vertebrales múltiples postsuspensión. Este evento es infrecuente y se lo atribuye a un rebote del remodelado óseo, postulándose se postula una predisposición especial, probablemente relacionada con microRNA. Se escriben dos mujeres con osteoporosis que presentaron este cuadro. Las fracturas ocurrieron entre 7 y 10 meses posteriores a la última dosis de denosumab. Registraron elevación de C-telopéptidos y disminución de la DMO conjuntamente con las fracturas vertebrales agudas en cascada. (AU)

The duration of osteoporosis treatments depends on the drug type, anabolic or anticatabolic, and the severity of the disease. Denosumab is a fully human monoclonal antibody that inactivates RANK-L, inhibiting the RANKL-RANK interaction . This inhibits osteoclast formation, activation, and survival. It also reduces cortical and trabecular bone resorption. Subcutaneous administration of 60 mg every 6 months for 3 years has reduced bone resorption, increased bone mineral density (BMD) and decreased vertebral, non-vertebral and hip fractures. It is indicated for the treatment of osteoporosis with high risk of fracture. Denosumab mechanism of action is reversible. After discontinuation, loss of BMD and elevation of bone turnover markers have been observed. In addition, multiple vertebral fractures after the suspension of the drug have been reported. These rebound-associated vertebral fractures are rare. A special genetic predisposition related to miRNA has been proposed. Two women with this clinical presentation are described. Fractures occurred between 7 and 10 months respectively after the last dose of denosumab. They presented with an increase in circulating C-telopeptid levels and a decrease inBMD with acute multiple vertebral fractures. (AU)

Evaluación de score de hueso trabecular (TBS) en pacientes menopáusicas con fracturas y sin ellas / Trabecular bone score evaluation in postmenopausal women with or without fractures

El score de hueso trabecular (TBS, Trabecular Bone Score) es una medición de la textura de los grises derivada de la evaluación del raquis por DXA y proporciona un índice de la microarquitectura ósea. Se ha demostrado que los valores bajos presentan capacidad para predecir fracturas. Nuestro objetivo fue evaluar si existían diferencias entre los valores de TBS de pacientes con fracturas frente a no fracturadas. Materiales y métodos: se revisaron 159 historias clínicas de mujeres menopáusicas que consultaron para evaluación de su salud ósea. Se consideraron los antecedentes autorreferidos de fracturas (Fx), la DMO de raquis, cuello femoral y fémur total y TBS. Resultados: treinta pacientes (18,9%) presentaron fracturas y en ellas se observó menor TBS (con Fx: 1,295±83 vs. sin Fx: 1,366±84, p<0,0001), menor índice de masa corporal (IMC) (con Fx: 23,7±1,9 vs. sin Fx: 25,7±4,2, p=0,02), sin diferencias en la edad (p=0,39), ni en valores de DMO (L1-L4 p=0,11, cuello femoral p=0,20 y fémur total p= 0,12). Muchas de las fracturas ocurrieron en pacientes sin osteoporosis por DXA. Conclusiones: el TBS aumentaría la capacidad de DXA para identificar a mujeres argentinas en riesgo de padecer fracturas sin tener osteoporosis densitométrica. Este es el primer trabajo realizado en la Argentina con medición de TBS. (AU)

Trabecular Bone Score (TBS) is a measure of the grey scale derived from DXA lumbar image and provides information about microarchitecture. It has been shown that low TBS values can predict fractures. Our objective was to evaluate if there are any differences between the TBS values in patients with fractures vs. non-fractures. Materials and methods: We reviewed 159 medical records of menopausal women who consulted for evaluation of their bone health. Self-reported fractures (Fx), spine BMD, femoral neck and total femur and TBS were evaluated. Results: thirty patients (18.9%) presented fractures and they showed lower TBS (with Fx: 1,295±0,083 vs. without Fx: 1,366±0,084, p<0.0001), lower body mass index (BMI) (with Fx: 23.7±1.9 vs. without Fx 25.7±4.2, p=0.02), without differences in ages (p=0.39) or in BMD values (L1-L4 p=0.11, femoral neck p=0.20 and total femur p=0.12). Some fractures occurred in patients without osteoporosis, as determined by DXA. Conclusions: TBS would increase the ability of DXA to identify Argentine women at risk for fractures without densitometric osteoporosis. This is the first work done in Argentina with TBS measurement. (AU)

Guías Argentinas para el diagnóstico, la prevención y el tratamiento de la osteoporosis 2015 / Argentine guidelines for the diagnosis, prevention and treatment of osteoporosis, 2015

La osteoporosis es una enfermedad en constante crecimiento y que afecta a más de 200 millones de personas a nivel mundial. Nuestras recomendaciones son guías para el diagnóstico, la prevención y tratamiento, pero no normas para las decisiones clínicas en casos individuales. El médico debe adaptarlas a situaciones en la práctica clínica cotidiana, incorporando factores personales que trascienden los límites de estas guías y hacen al saber y al arte de la práctica médica. Como todo conocimiento científico, deben ser actualizadas periódicamente a medida que se adquieran nuevas, mejores y más efectivas herramientas diagnósticas y terapéuticas. (AU)

Osteoporosis is an evolving disease which affects over 200 million people worldwide. Our recommendations are guidelines for its diagnosis, prevention and treatment, but they do not constitute standards for clinical decisions in individual cases. The physician must adapt them to individual special situations, incorporating personal factors that transcend the limits of these guidelines and are dependent on the knowledge and art of the practice of Medicine. These guidelines should be reviewed and updated periodically as new, better and more effective diagnostic and therapeutic tools become available. (AU)

Evaluación de la respuesta densitométrica en pacientes con osteoporosis posmenopáusica tratadas con ranelato de estroncio o denosumab / Densitometric response in postmenopausal osteoporosis treated with strontium ranelate or denosumab

Tanto el ranelato de estroncio (RSr) como el denosumab (Dmab) son eficaces en el tratamiento de la osteoporosis (OP) posmenopáusica (PM). El efecto de cada fármaco por separado sobre la densidad mineral ósea (DMO) ha sido estudiado recientemente. Con ambas drogas se observó, al año de tratamiento, un aumento significativo de la DMO en columna lumbar (CL), cuello femoral (CF) y cadera total (CT). En este trabajo comparamos la respuesta densitométrica al año de tratamiento con una y otra droga. Utilizamos los registros de 425 pacientes PMOP tratadas con Dmab y 441 tratadas con RSr. En cada paciente analizamos el porcentaje de cambio; se clasificaron como respondedoras aquellas que mostraron un cambio ≥3%. Adicionalmente se comparó la respuesta en pacientes no previamente tratadas con bifosfonatos (BF-naïve) en comparación con pacientes que habían recibido previamente un BF. Al analizar el grupo completo para Dmab, el porcentaje de pacientes respondedoras fue de 68,4% en CL, 63,3% en CF y 49,3% en CT. Por otro lado, en el grupo de pacientes tratadas con RSr, el porcentaje de respondedoras (53,8% en CL, 40,0% en CF y 35,6% en CT) fue estadísticamente menor. Cuando comparamos la respuesta entre las pacientes BF-naïve que recibieron RSr o Dmab, el Dmab indujo mayor respuesta en CL y CF que el grupo RSr, sin diferencias en CT. Cuando se analizaron los subgrupos BF-previo, las tratadas con Dmab mostraron mayor respuesta en todas las regiones. Conclusión: en pacientes con OP-PM, el tratamiento con Dmab produjo mayores incrementos densitométricos que el RSr, siendo el porcentaje de pacientes respondedoras mayor con Dmab que con RSr. (AU)

Both strontium ranelate (SrR) and denosumab (Dmab) are effective in the treatment of postmenopausal osteoporosis (PMOP). The effect of each drug on bone mineral density (BMD) has been studied separately by us. With both treatments, there was a significant increase after one year of treatment at the lumbar spine (LS) and hip. In this paper we compared the densitometric response after one year of treatment with both drugs used separately. We used the clinical records of 425 PM patients treated with Dmab and 441 treated with SrR. For each patient we analyzed the percentage of change; those who showed a change ≥3% were classified as responders. Additionally, the response was compared in patients not previously treated with bisphosphonates (BP-naïve) compared to patients who had previously received a BP. When analyzing the complete group for Dmab, the percentage of "responders" was 65.2% at the LS, 62.9% at the femoral neck (FN) and 47.4% at the total hip (TH). On the other hand, in the group of patients treated with SrR the percentage of responders (53.8% at the LS, 40.0% at the FN and 35.6% at the TH) was statistically lower. When comparing the response between in BF-naïve patients receiving RSr or Dmab, Dmab induced a greater response at the LS and FN than the RSr group, with no statistical differences at the TH. When the subgroups with prior BP treatment were analyzed, those treated with Dmab showed greater response in all regions. Conclusion: in patients with PMOP treatment with Dmab produced greater densitometric increments than SrR, and the percentage of responders was higher with Dmab than with SrR. (AU)

Hipercalcemia hipocalciurica familiar en una paciente con mutación del receptor de calcio: forma atípica de presentación y tratamiento con cinacalcet / Familial hypocalciuric hypercalcemia in a patient with calcium-sensing receptor mutation: atypical clinical presentation and treatment with cinacalcet

El hiperparatiroidismo familiar y la hipercalcemia hipocalciúrica familiar (HHF) constituyen un subgrupo heterogéneo de trastornos con herencia mendeliana, que representan en conjunto el 5% de las causas de hipercalcemia PTH dependiente. La HHF se asocia con mutaciones del gen del receptor sensor de calcio (CaSR). Esta entidad se manifiesta, en la mayoría de los casos, con la presentación asintomática y familiar de hipercalcemia e hipocalciuria y valores elevados o normales de hormona paratiroidea (PTH). Los avances en la biología molecular han contribuido al diagnóstico, evaluación del fenotipo de cada entidad y elección del tratamiento. Se describe el caso de una paciente con hipercalcemia estudiada a partir de una tumoración de cuello asociada con una glándula paratiroides quística. Luego de un exhaustivo proceso diagnóstico se halló en el estudio genético una mutación inactivante en el gen CaSR. Teniendo en cuenta la presencia de la relación clearance calcio/clearance creatinina <0,01 y la falta de respuesta al tratamiento quirúrgico, se consideró la entidad de HHF con forma de presentación atípica. La paciente, sin tratamiento, presentaba un progresivo incremento de la calcemia luego de la cirugía de las glándulas paratiroides, que no se controló con el uso de bifosfonatos y evolucionó con episodios de mareos y desmayos frecuentes sin causa neurológica o cardiovascular detectada. Por lo tanto, se inició el tratamiento con cinacalcet, con el cual se obtuvo una buena respuesta terapéutica: descenso de la calcemia y mejoría de la sintomatología luego de un año de su comienzo. El cinacalcet es una herramienta terapéutica de importancia en estos raros casos de HHF. (AU)

Familial hyperparathyroidism including familial hypocalciuric hypercalcemia (FHH) is an heterogeneous subgroup of disorders with Mendelian inheritance, that account for 5% of PTH dependent hypercalcemia. FHH is associated with mutations of the calcium receptor (CaSR) gene. This entity is manifested by hypercalcemia with hypocalciuria and high or normal levels of parathyroid hormone (PTH) generally asymptomatic and with familial presentation. Advances in molecular biology have contributed to the diagnosis, evaluation of the phenotype of each entity and the choice of treatment. We describe a patient with hypercalcemia diagnosed following the finding of a neck tumor associated with cystic parathyroids. After an exhaustive diagnostic process, an inactivating mutation in the CaSR gene was found. Considering the presence of a ratio clearance calcium / clearance creatinine <0.01 and the lack of response to surgical treatment, HHF entity with atypical presentation was considered. The patient exhibited progressive increase in serum calcium following parathyroid surgery, which was not controlled with the use of bisphosphonates and evolved into episodes of frequent dizziness and fainting, without neurological or cardiovascular causes. Treatment with cinacalcet was initiated, with a good therapeutic response. The use of cinacalcet is a useful therapeutic tool in these rare cases of FHH. (AU)

Ranelato de estroncio: tratamiento para osteoporosis: [revisión] / Strontium ranelate in the treatment of osteoporosis: [review]

El estroncio es un catión divalente que incrementa la formación ósea y disminuye la resorción.Este mecanismo de acción dual, disociando el remodelado, puede explicarse por su acción anivel del receptor sensor de calcio de osteoblastos, estimulando la diferenciación y actividad deosteoblastos e inhibiendo diferenciación y la acción de osteoclastos vía receptor RANK-L (ligandodel receptor del activador nuclear del factor kB). Es efectivo para reducir las fracturas vertebralesy no vertebrales en pacientes menopáusicas. Disminuye la incidencia de fracturas de cadera enpacientes >74 años con factores de riesgo adicionales. Se ha demostrado persistencia de suacción luego de 8 años de tratamiento. La acumulación de estroncio en el tejido óseo es progresivahasta alcanzar un máximo al tercer año de tratamiento. La eliminación del mismo, al terminar laterapia, puede inferirse por el cambio de los marcadores bioquímicos al tercer mes de suspendido,sugiriendo que la droga es eliminada rápidamente. Se administra en forma de suspensión oral,tiene buena tolerancia y los efectos adversos son leves, similares al placebo.Es una buena opción para el tratamiento de osteoporosis.

Bone and mineral metabolism in primiparous women and its relationship with breastfeeding: a longitudinal study.

The aim of this study was to evaluate the changes in bone metabolism in breastfeeding women (BF). We selected 30 primiparous women and compared them to 31 nulliparous women. We assessed bone mineral density (BMD) in the lumbar spine (LS), femoral neck (FN) and trochanter (TROC), biochemical parameters of bone turnover and hormone and cytokine levels at the puerperium, 6 months and 12 months after delivery. A trend to lower BMD of LS was seen at initial evaluation in BF. BMD in LS, FN, and TROC were increased 12 months after delivery. Baseline body mass index was higher in puerperal women (p = 0.02) and correlated with an increased FN and TROC BMD one year post delivery (p = 0.001 and p = 0.003). An increase in bone remodeling markers, and lower urinary calcium was observed; after 12 months these values normalized. Prolactin, parathormone related peptide (PTHrP) and IL-6 were enhanced during the first six months of breastfeeding. We conclude that calcium for breastfeeding was obtained by transient mobilization of calcium deposits from the trabecular bone, and urinary calcium sparing induced by calciotrophic hormones and cytokines. Body weight is an important factor in proximal femur BMD.

Bone and mineral metabolism in primiparous women and its relationship with breastfeeding: a longitudinal study / Metabolismo óseo y mineral en mujeres primíparas y su relación con la lactancia: un estudio longitudinal

The aim of this study was to evaluate the changes in bone metabolism in breastfeeding women (BF). We selected 30 primiparous women and compared them to 31 nulliparous women. We assessed bone mineral density (BMD) in the lumbar spine (LS), femoral neck (FN) and trochanter (TROC), biochemical parameters of bone turnover and hormone and cytokine levels at the puerperium, 6 months and 12 months after delivery. A trend to lower BMD of LS was seen at initial evaluation in BF. BMD in LS, FN, and TROC were increased 12 months after delivery. Baseline body mass index was higher in puerperal women (p = 0.02) and correlated with an increased FN and TROC BMD one year post delivery (p = 0.001 and p = 0.003). An increase in bone remodeling markers, and lower urinary calcium was observed; after 12 months these values normalized. Prolactin, parathormone related peptide (PTHrP) and IL-6 were enhanced during the first six months of breastfeeding. We conclude that calcium for breastfeeding was obtained by transient mobilization of calcium deposits from the trabecular bone, and urinary calcium sparing induced by calciotrophic hormones and cytokines. Body weigth is an important factor in proximal femur BMD.

El objetivo de este estudio fue evaluar los cambios que suceden en el metabolismo óseo de mujeres que amamantan. Se seleccionaron 30 mujeres primíparas y se compararon con 30 mujeres nulíparas como grupo control. Se evaluó la densidad mineral ósea (DMO) del raquis lumbar (RL), cuello femoral (CF) y trocánter (TROC), parámetros del remodelado óseo, hormonas y citoquinas. Estos parámetros se midieron en el puerperio inmediato, y a los 6 y 12 meses post-parto. La DMO del RL de la mujeres primíparas evidenciaron una tendencia a menores valores al comienzo de la lactancia comparadas con las mujeres controles, y se observó un incremento significativo de la DMO a los 12 meses, alcanzando valores similares al grupo control. La DMO en CF y del TROC aumentó significativamente a los 12 meses post parto. El índice de masa corporal basal fue mayor en el grupo de primíparas en el puerperio inmediato (p = 0.02) y correlacionó con el incremento observado en la DMO CF y del TROC al año del post-parto (p = 0.001 y p = 0.003, respectivamente). Un alto remodelado óseo y descenso en el calcio urinario se observaron en el puerperio inmediato, y tanto los marcadores óseos como la calciuria se normalizaron a los 12 meses post-parto. Prolactina, interleuquina-6 y el PTHrP aumentaron significativamente en los primeros 6 meses. Concluimos que el calcio de la leche materna proviene de la movilización de los depósitos cálcicos del hueso trabecular y del ahorro de la pérdida renal inducido por las hormonas calcitrópicas y las citoquinas involucradas en el metabolismo óseo. El peso corporal es un factor de importancia en el incremento de DMO del fémur proximal.

Densidad mineral ósea de raquis y cadera, y variables de resistencia ósea por DXA / Bone mineral density at the spine and hip, and bone resistance parameters calculated from DXA measurements

La densidad mineral ósea evaluada por DXA predice el riesgo de fractura de cadera. Los pacientes añosos, aún con densitometría normal pueden fracturarse. Esto indica que otras propiedades del hueso, participan en la resistencia ósea, como las características físicas del material y la geometría. Nuestro objetivo fue evaluar mujeres normales de la ciudad de Buenos Aires con las nuevas tecnologías DXA y medir los parámetros geométricos y arquitectónicos. Evaluamos 903 mujeres con equipo GE Lunar Prodigy. La edad media fue 55 ± 7.23 años y la talla 1.60 ± 0.06 m. Esta descendió progresivamente con la edad, siendo 1.54±0.05 m en las mayores de 70a. La DMO media de L1-L4, en mujeres jóvenes fue 1.16 ± 0.12 g/cm2, en cuello femoral, 0.93 ±0.1g/cm2, cuello superior 0.81 ± 0.13 g/cm2 y fémur total 0.95 ± 0.09 g/cm2. Los valores de DMO también descendieron progresivamente. La media de longitud del eje de cadera (HAL) fue 103.12 ±5.71 mm y mostró marcada correlación con la talla y no con edad. El momento de inercia de la sección cruzada (CSMI) correlacionó con la DMO. Las variables geométricas permanecieron estables con el tiempo, demostrando condicionamiento genético, en tanto las arquitectónicas se modificarían por el remodelado durante la vida. Nuestros datos demuestran que la mujer argentina presenta valores arquitectónicos y geométricos en fémur proximal similares a los descriptos en la literatura. La asociación de los mismos permitirá una mejor evaluación de los individuos en riesgo.

Congenital adrenal hyperplasia clinical characteristics and genotype in newborn, childhood and adolescence.

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a disorder which can adopt three clinical expressions: two classical forms -salt-wasting (SW), with residual enzymatic activity (EA) < or = 1% and simple virilizing (SV), with EA 1-2%- and a mild late onset or nonclassical (NC) form, with EA 10-60%. Our objective is to describe clinical characteristics, growth, and bone mass in a group of patients affected by 21-hydroxylase deficiency. Besides, molecular genetics studies were performed in patients, and also when available in their parents and siblings. Nine patients with neonatal diagnosis and 8 with pre or postpubertal diagnosis were studied. Analyses of 10-point mutations in the CYP21A2 gene were performed. We found that all the patients with the classical expression, except one with a de novo mutation R356W in one allele, were fully genotyped with predictive < 2% EA mutations. Signs of hyperandrogenism were present in 5/6 NC patients; one was diagnosed by searching for mutations in asymptomatic siblings. All the NC patients were compound heterozygotes carrying V281L mutation in one allele and a predictive low EA in the other, except for one not yet determined. In patients with neonatal diagnosis, mean height was low at one year of age, though it showed a significant increase before the onset of puberty. We conclude that neonatal diagnosis of classical CAH allows an adequate follow up enhancing growth. Molecular analyses of all members of an affected family may disclose asymptomatic patients. The presence of de novo mutations, as well as, the presence of mutations with low predicted EA in NC patients reinforces the importance of genotyping for appropriate genetic counseling. In fully genotyped NC patients, the lowest value of ACTH-stimulated 17OHP was 14 ng/ml. Lower cut-off values might overestimate the diagnosis of the NC form.

Congenital adrenal hyperplasia clinical: characteristics and genotype in newborn, childhood and adolescence / Hiperplasia suprarrenal congenital: características clínicas, seguimiento y genotipo en la etapa perinatal, la niñez y la adolescencia

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a disorder which can adopt three clinical expressions: two classical forms –salt-wasting (SW), with residual enzymatic activity (EA) < 1% and simple virilizing (SV), with EA 1-2%– and a mild late onset or nonclassical (NC) form, with EA 10-60%. Our objective is to describe clinical characteristics, growth, and bone mass in a group of patients affected by 21-hydroxylase deficiency. Besides, molecular genetics studies were performed in patients, and also when available in their parents and siblings. Nine patients with neonatal diagnosis and 8 with pre or postpubertal diagnosis were studied. Analyses of 10-point mutations in the CYP21A2 gene were performed. We found that all the patients with the classical expression, except one with a de novo mutation R356W in one allele, were fully genotyped with predictive < 2% EA mutations. Signs of hyperandrogenism were present in 5/6 NC patients; one was diagnosed by searching for mutations in asymptomatic siblings. All the NC patients were compound heterozygotes carrying V281L mutation in one allele and a predictive low EA in the other, except for one not yet determined. In patients with neonatal diagnosis, mean height was low at one year of age, though it showed a significant increase before the onset of puberty. We conclude that neonatal diagnosis of classical CAH allows an adequate follow up enhancing growth. Molecular analyses of all members of an affected family may disclose asymptomatic patients. The presence of de novo mutations, as well as, the presence of mutations with low predicted EA in NC patients reinforces the importance of genotyping for appropriate genetic counseling. In fully genotyped NC patients, the lowest value of ACTH-stimulated 17OHP was 14 ng/ml. Lower cut-off values might overestimate the diagnosis of the NC form.

La hiperplasia suprarrenal congénita por déficit de 21-hidroxilasa presenta tres formas clínicas: dos clásicas, perdedora de sal, con actividad enzimática (AE) < 1% y virilizante simple, con AE 1-2% y una no clásica, con AE 10-60%. Nuestro objetivo es describir las características clínicas y el genotipo de un grupo de pacientes con hiperplasia suprarrenal congénita; este último también sedeterminó en todos los miembros de la familia. Se estudiaron 9 pacientes diagnosticados en la etapa perinatal y 8 durante la etapa pre y postpuberal. Se analizaron diez mutaciones en el gen CYP21A2 y se evaluó crecimiento y densidad mineral ósea. Once pacientes presentaron la forma clásica: 9 con diagnóstico perinatal y 2 diagnosticados más tardíamente, uno de ellos con agrandamiento testicular por restos adrenales. Todos los pacientes, salvo 1 con una mutación de novo R356W en un alelo, presentaron ambos alelos mutados con un genotipo que predice AE < 2%. Seis pacientes presentaron la forma no clásica, todos con signos clínicos de hiperandrogenismo salvo un familiar asintomático que se diagnosticó por el estudio molecular. Todos, a excepción de uno con un alelo aún no determinado, presentaron la mutación V281L acompañada de otra que predice AE < 2%. Durante la evolución de los pacientes de diagnóstico perinatal se observó talla baja al año con recuperación de la misma en la etapa prepuberal. La densidad mineral ósea fue normal. Podemos concluir que el diagnóstico en la etapa perinatal en pacientes con la forma clásica posibilita un mejor seguimiento y crecimiento. La genotipificación de todos los miembros de una familia permite el diagnóstico de formas asintomáticas. La presencia de mutaciones de novo y de un alelo con una mutación que predice baja AE en los pacientes con forma no clásica, refuerza la importancia de la genotipificación para un adecuado asesoramiento genético.

Congenital adrenal hyperplasia clinical: characteristics and genotype in newborn, childhood and adolescence / Hiperplasia suprarrenal congenital: características clínicas, seguimiento y genotipo en la etapa perinatal, la niñez y la adolescencia

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a disorder which can adopt three clinical expressions: two classical forms ¹salt-wasting (SW), with residual enzymatic activity (EA) < 1% and simple virilizing (SV), with EA 1-2%¹ and a mild late onset or nonclassical (NC) form, with EA 10-60%. Our objective is to describe clinical characteristics, growth, and bone mass in a group of patients affected by 21-hydroxylase deficiency. Besides, molecular genetics studies were performed in patients, and also when available in their parents and siblings. Nine patients with neonatal diagnosis and 8 with pre or postpubertal diagnosis were studied. Analyses of 10-point mutations in the CYP21A2 gene were performed. We found that all the patients with the classical expression, except one with a de novo mutation R356W in one allele, were fully genotyped with predictive < 2% EA mutations. Signs of hyperandrogenism were present in 5/6 NC patients; one was diagnosed by searching for mutations in asymptomatic siblings. All the NC patients were compound heterozygotes carrying V281L mutation in one allele and a predictive low EA in the other, except for one not yet determined. In patients with neonatal diagnosis, mean height was low at one year of age, though it showed a significant increase before the onset of puberty. We conclude that neonatal diagnosis of classical CAH allows an adequate follow up enhancing growth. Molecular analyses of all members of an affected family may disclose asymptomatic patients. The presence of de novo mutations, as well as, the presence of mutations with low predicted EA in NC patients reinforces the importance of genotyping for appropriate genetic counseling. In fully genotyped NC patients, the lowest value of ACTH-stimulated 17OHP was 14 ng/ml. Lower cut-off values might overestimate the diagnosis of the NC form.(AU)

La hiperplasia suprarrenal congénita por déficit de 21-hidroxilasa presenta tres formas clínicas: dos clásicas, perdedora de sal, con actividad enzimática (AE) < 1% y virilizante simple, con AE 1-2% y una no clásica, con AE 10-60%. Nuestro objetivo es describir las características clínicas y el genotipo de un grupo de pacientes con hiperplasia suprarrenal congénita; este último también sedeterminó en todos los miembros de la familia. Se estudiaron 9 pacientes diagnosticados en la etapa perinatal y 8 durante la etapa pre y postpuberal. Se analizaron diez mutaciones en el gen CYP21A2 y se evaluó crecimiento y densidad mineral ósea. Once pacientes presentaron la forma clásica: 9 con diagnóstico perinatal y 2 diagnosticados más tardíamente, uno de ellos con agrandamiento testicular por restos adrenales. Todos los pacientes, salvo 1 con una mutación de novo R356W en un alelo, presentaron ambos alelos mutados con un genotipo que predice AE < 2%. Seis pacientes presentaron la forma no clásica, todos con signos clínicos de hiperandrogenismo salvo un familiar asintomático que se diagnosticó por el estudio molecular. Todos, a excepción de uno con un alelo aún no determinado, presentaron la mutación V281L acompañada de otra que predice AE < 2%. Durante la evolución de los pacientes de diagnóstico perinatal se observó talla baja al año con recuperación de la misma en la etapa prepuberal. La densidad mineral ósea fue normal. Podemos concluir que el diagnóstico en la etapa perinatal en pacientes con la forma clásica posibilita un mejor seguimiento y crecimiento. La genotipificación de todos los miembros de una familia permite el diagnóstico de formas asintomáticas. La presencia de mutaciones de novo y de un alelo con una mutación que predice baja AE en los pacientes con forma no clásica, refuerza la importancia de la genotipificación para un adecuado asesoramiento genético.(AU)