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)

Argentine Guidelines for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis in Postmenopausal Women and Men Aged 50 Years and Older.

OBJECTIVE: The aim of this study was to provide an evidence-based framework to guide health care professionals treating patients under glucocorticoid (GC) therapy and develop guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis (GIO) in postmenopausal women and men aged ≥50 years. METHODS: An expert panel on bone diseases designed a series of clinically meaningful questions following the PICO (Population, Intervention, Comparator, and Outcome) structure. Using GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology, we made a systematic literature review, extracted and summarized the effect estimates, and graded the quality of the evidence. The expert panel voted each PICO question and made recommendations after reaching an agreement of at least 70%. RESULTS: Seventeen recommendations (9 strong and 8 conditional) and 8 general principles were developed for postmenopausal women and men aged ≥50 years under GC treatment. Bone mineral density (BMD), occurrence of fragility fractures, probability of fracture at 10 years by Fracture Risk Assessment Tool, and other screening factors for low BMD are recommended for patient evaluation and stratification according to fragility fracture risk. The treatment of patients under GC therapy should include counseling on lifestyle habits and strict control of comorbidities. The goal of GIO treatment is the nonoccurrence of new fragility fractures as well as to increase or maintain BMD in certain clinical situations. This was considered for the therapeutic approach in different clinical scenarios. CONCLUSIONS: This GIO guideline provides evidence-based guidance for health care providers treating patients.

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.

Is sarcopenia a risk factor for rotator cuff tears?

BACKGROUND: Sarcopenia is the loss of muscle mass and consequent loss of muscle function with aging. Currently, it is considered an independent risk factor for falls and fractures, disability, postoperative complications, and mortality. Rotator cuff tears are known to be influenced by systemic diseases such as diabetes mellitus, hypercholesterolemia, thyroid disease, and osteoporosis. The aim of our study was to determine if there is a correlation between sarcopenia prevalence and rotator cuff tears. METHODS: This is a prospective case-control study. Between May 2017 and May 2018, 106 patients were evaluated and divided into 2 groups. Group 1 (cases) included 53 consecutive patients with chronic symptomatic full-thickness rotator cuff tears (mean age, 72 ± 5 years), and group 2 (controls) included 53 patients without rotator cuff tears (mean age, 71 ± 6 years). Sarcopenia was diagnosed with the presence of 2 of 3 criteria: low skeletal muscle mass, inadequate muscle strength, and inadequate physical performance. Rotator cuff integrity was evaluated with magnetic resonance imaging in all patients. RESULTS: No significant differences were found in baseline data and demographic factors between the groups, except for the smoking habit (P = .02). The prevalence of sarcopenia was not significantly different between the groups, nor were gait speed, grip strength, and skeletal muscle mass index (P = .15, .99, and .9, respectively). CONCLUSION: The prevalence of sarcopenia in patients with rotator cuff tears was similar to an age- and sex-matched control population. Thus, with these results, we are not able to consider sarcopenia as an independent risk factor for rotator cuff tears.

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)

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

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.

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 en todo el mundo. 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.

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.

Osteosclerosis asociada a mastocitosis sistémica / Osteosclerosis associated to systemic mastocytosis / Osteosclerose associada a mastocitose sistêmica

La mastocitosis es una enfermedad rara que se define por la expansión anormal de los mastocitos clonales y su acumulación en distintos tejidos. Esta enfermedad afecta el esqueleto en el 50-70% de los casos. Las anomalías radiológicas son generalmente difusas y afectan predominantemente al esqueleto axial. La forma más habitual es la osteopenia. La osteosclerosis y las formas mixtas son menos frecuentes. Se presenta el caso de un paciente varón de 74 años, con osteoesclerosis asociada a mastocitosis sistémica. Se observó un incremento de los marcadores de formación y resorción, con predominio de los primeros. La densitometría ósea presentó un notable incremento y en los estudios radiológicos se observó osteoesclerosis. La biopsia ósea transilíaca evidenció infiltrados multifocales de mastocitos y fibrosis de la médula ósea. La histomorfometría mostró un incremento en los parámetros de formación y en menor grado de la resorción ósea. Se indicó loratadina, corticoesteroides, interferón alfa, calcio y calcitriol. Se observó mejoría clínica, normalización de los marcadores de remodelación y disminución de la densidad mineral ósea 30 meses después de iniciado el tratamiento. Se destaca la importancia de considerar la mastocitosis sistémica en el diagnóstico diferencial de pacientes con osteoesclerosis u osteoporosis.

Mastocytosis is a rare disease defined by abnormal clonal mast-cell expansion and accumulation in various tissues. The disease affects the skeleton in 60-70% of cases. Radiological abnormalities are usually diffuse and the lesions mainly involve the axial skeleton. Osteopenia is the most frequent form, but it can also occur as osteosclerosis or a combination of both disease expressions. In this report, a 74-year old male patient with osteosclerosis associated to systemic mastocytosis is presented. Laboratory tests showed an elevation in bone turnover markers with a greater increase in bone formation markers. Bone densitometry depicted a marked increase in mineral density and X-rays showed osteoesclerosis. A trans-iliac bone biopsy described the presence of dense, multifocal infiltrates of mast cells and bone marrow fibrosis. Bone histomorphometry showed a marked increase in bone formation and resorption parameters. Treatment with loratadine, corticosteroids, á interferon, calcium and calcitriol was initiated. The patient improved, bone turnover markers normalized and bone mineral density decreased after 30 months. The importance of considering systemic mastocytosis in the differential diagnosis of patients with osteosclerosis or osteoporosis.

A mastocitose é uma doença rara que se define pela expansão anormal dos mastócitos clonais e sua acumulação em diferentes tecidos. Esta doença afeta o esqueleto em 50-70% dos casos. As anomalias radiológicas geralmente são difusas e afetam predominantemente o esqueleto axial. A forma mais habitual é a osteopenia. A osteosclerose e as formas mistas são menos frequentes. Apresenta-se o caso de um paciente masculino de 74 anos, com osteosclerose associada a mastocitose sistêmica. Foi observado um incremento dos marcadores de formação e reabsorção, com predomínio dos primeiros. A densitometria óssea apresentou importante incremento e nos estudos radiológicos foi observada osteosclerose. A biópsia óssea transilíaca evidenciou infiltrados multifocais de mastócitos e fibrose da medula óssea. A histomorfometria mostrou um aumento nos parâmetros de formação e, em menor grau, da reabsorção óssea. Indicou-se loratadina, corticoesteroides, interferón-alfa, cálcio e calcitriol. Foi observada a melhoria clínica, normalização dos marcadores de remodelação e diminuição da densidade mineral óssea 30 meses depois de iniciado o tratamento. Destaca-se a importância de considerar a mastocitose sistêmica no diagnóstico diferencial de pacientes com osteosclerose ou osteoporose.

Strontium ranelate effect on bone mineral density is modified by previous bisphosphonate treatment.

The aim of this study was to evaluate the effect of strontium ranelate (SrR) on bone mineral density (BMD) and bone turnover markers after 1 year of treatment. Additionally, the effect of SrR in bisphosphonate-naïve patients (BP-naïve) compared to patients previously treated with bisphosphonates (BP-prior) was analyzed. This retrospective study included 482 postmenopausal women treated with SrR (2 g/day) for 1 year in ten Argentine centers; 41 patients were excluded due to insufficient data, while 441 were included. Participants were divided according to previous bisphosphonate treatment in two groups: BP-naïve (n = 87) and BP-prior (n = 350). Data are expressed as mean ± SEM. After 1 year of treatment with SrR the bone formation markers total alkaline phosphatase and osteocalcin were increased (p < 0.0001), while the bone resorption marker s-CTX was decreased (p = 0.0579). Also increases in BMD at the lumbar spine (LS, 3.73%), femoral neck (FN, 2.00%) and total hip (TH, 1.54%) [p < 0.0001] were observed. These increments were significant (p < 0.0001) both among BP-naïve and BP-prior patients. Interestingly, the change in BMD after 1 year of SrR treatment was higher in BP-naïve patients: LS: BP-naïve = 4.58 ± 0.62%; BP-prior = 3.45 ± 0.28% (p = 0.078). FN: BP-naïve = 2.79 ± 0.56%; BP-prior = 2.13 ± 0.29% (p = 0.161). TH: BP-naïve = 3.01 ± 0.55%; BP-prior = 1.22 ± 0.27% (p = 0.0006). SrR treatment increased BMD and bone formation markers and decreased a bone resorption marker in the whole group, with better response in BP-naïve patients.

Assessment of bone microarchitecture in postmenopausal women on long-term bisphosphonate therapy with atypical fractures of the femur.

Reports of atypical femoral fractures (AFFs) in patients receiving long- term bisphosphonate therapy have raised concerns regarding the genesis of this rare event. Using high-resolution peripheral quantitative computed tomography (HR-pQCT), we conducted a study to evaluate bone microarchitecture in patients who had suffered an AFF during long-term bisphosphonate treatment. The aim of our study was to evaluate if bone microarchitecture assessment could help explain the pathophysiology of these fractures. We compared bone volumetric density and microarchitectural parameters measured by HR-pQCT in the radius and tibia in 20 patients with AFFs with 35 postmenopausal women who had also received long-term bisphosphonate treatment but had not experienced AFFs, and with 54 treatment-naive postmenopausal women. Control groups were similar in age, body mass index (BMI), and bone mineral density (BMD). Mean age of the 20 patients with AFFs was 71 years, mean lumbar spine T-score was -2.2, and mean femoral neck T-score was -2. Mean time on bisphosphonate treatment was 10.9 years (range, 5-20 years). None of the patients had other conditions associated with AFFs such as rheumatoid arthritis, diabetes or glucocorticoid use. There were no statistically significant differences in any of the parameters measured by HR-pQCT between postmenopausal women with or without treatment history and with or without history of atypical fractures. We could not find any distinctive microarchitecture features in the peripheral skeleton of women who had suffered an atypical fracture of the femur while receiving bisphosphonate treatment. This suggests that risk of developing an atypical fracture is not related to bone microarchitecture deterioration. Our results indicate that there may be other individual factors predisposing to atypical fractures in patients treated with bisphosphonates, and that those are independent of bone microarchitecture. In the future, identification of those factors could help prevent and understand the complex physiopathology of these rare events.

Sarcopenia: una entidad de relevancia clínica actual en adultos mayores / Sarcopenia: an entity of current clinical relevance in older adults

La sarcopenia se define como la pérdida progresiva y gradual de la masa, la función y la fuerza del músculo esquelético que se presenta durante elproceso del envejecimiento. Todavía está en discusión hasta qué punto se puede considerar como un efecto deletéreo propio de la edad o como unsíndrome geriátrico con repercusiones clínicas, daño funcional e incapacidad. Lo que es realmente fundamental es que la pérdida de la masa muscularesquelética contribuye a un mayor riesgo de discapacidad física, fragilidad, pérdida de la independencia, pobre calidad de vida, incremento en los costos para el cuidado de la salud y aumento en la tasa de mortalidad de las personas envejecidas. Su etiología es compleja y multifactorial.Recientemente diversos grupos de trabajo han centrado su interés en la investigación en el área de la sarcopenia, debido a las consecuencias que tiene en la salud y funcionalidad del adulto mayor. El objetivo de esta revisión es examinar la información disponible sobre la conceptualización, definición y métodos de diagnóstico de la sarcopenia. Se mencionan los métodos de determinación de la masa muscular esquelética por técnicas de imagen como la resonancia magnética y la absorciometría dual de energía de rayos X (DXA). Se considera su estimación a través de análisis de impedancia bioeléctrica y de ecuaciones de predicción. Se mencionan los puntos de corte que se han utilizado con mayor frecuencia para el diagnóstico de sarcopenia y, asimismo, se muestra su prevalencia en diversos estudios epidemiológicos y las propuestas de tratamientos actuales.