Bone effects of epidural and intra-articular glucocorticoids: a systematic literature review / Efectos óseos de los glucocorticoides epidurales e intraarticulares: revisión sistemática de la literatura

Osteoporosis and vertebral and non-vertebral fractures are common in glucocorticoids (GC) treated patients. Oral GC treatment leads to bone loss, particularly of trabecular bone. The benefits of GC used in rheumatological and traumatological disorders are known but they would have possible negative effects on bone. This systematic review aimed to evaluate the effects of epidural steroid injections (ESI), and intra-articular and intramuscular GC administration on bone mineral density (BMD) and fragility fractures. A systematic review of Medline/PubMed, Cochrane, and LILACS up to November 2020 was conducted. Meta-analyses, systematic reviews, randomized and non-randomized controlled trials, and prospective and retrospective studies comparing the effect of ESI, intra-articular or intramuscular GC used compared to a control group or baseline measurements were included. Results: A total of 8272 individuals were included among the 13 selected articles (10 about ESI and 3 about intra-articular GC; no article was found evaluating intramuscular GC). Only a few studies showed a negative effect of ESI on bone in the qualitative analysis considering osteopenia and osteoporosis in lumbar spine, femoral neck and total hip and BMD as surrogate outcomes. On the other hand, the qualitative analysis showed that most studies found an increased risk of fragility fracture. However, only two studies could be included in the quantitative analysis, in which there were no differences between patients exposed to ESI versus controls in all evaluated regions. In conclusion, there was insufficient evidence to suggest that ESI and intra-articular GC, unlike oral GC, negatively affect bone mass. Longitudinal studies are needed to obtain more knowledge regarding the effect of ESI or intra-articular GC on BMD and fragility fractures. (AU)

La osteoporosis y las fracturas vertebrales y no vertebrales son comunes en pacientes tratados con glucocorticoides (GC). El tratamiento oral con GC conduce a la pérdida ósea, particularmente del hueso trabecular. Los beneficios de los GC utilizados en patologías reumatológicas y traumatológicas son conocidos, pero tendrían posibles efectos negativos sobre el hueso. Esta revisión sistemática tuvo como objetivo evaluar los efectos de las inyecciones epidurales de esteroides (ESI), GC intraarticulares e intramusculares sobre la densidad mineral ósea (DMO) y las fracturas por fragilidad. Se realizó una revisión sistemática de Medline/PubMed, Cochrane y LILACS hasta noviembre de 2020. Se incluyeron metanálisis, revisiones sistemáticas, ensayos controlados aleatorizados y no aleatorizados, estudios prospectivos y retrospectivos que compararon el efecto de ESI, GC intraarticular o intramuscular utilizado en comparación con un grupo de control o mediciones iniciales. Resultados: Se incluyeron un total de 8272 individuos entre los 13 artículos seleccionados (10 sobre ESI y 3 sobre GC intraarticular; no se encontró ningún artículo que evaluara GC intramuscular). Solo unos pocos estudios mostraron un efecto negativo del ESI sobre el hueso en el análisis cualitativo considerando la osteopenia y la osteoporosis en la columna lumbar, el cuello femoral y la cadera total y la DMO como un resultado indirecto. Por otro lado, el análisis cualitativo mostró que la mayoría de los estudios encontraron un mayor riesgo de fractura por fragilidad. Sin embargo, solo dos estudios pudieron incluirse en el análisis cuantitativo, en los que no hubo diferencias entre los pacientes expuestos a ESI versus los controles en todas las regiones evaluadas. En conclusión, no hallamos datos suficientes para sugerir que la ESI y los GC intraarticulares, a diferencia de los GC orales, afectan negativamente a la pérdida ósea. Se necesitan estudios longitudinales para obtener más conocimiento sobre el efecto de ESI o GC intraarticular en la DMO y las fracturas por fragilidad. (AU)

Association between fractures and traditional risk factors for osteoporosis and low bone mineral density in patients with obesity

ABSTRACT Objective: To evaluate the reasons for request of bone mineral density (BMD) evaluation and correlate the BMD results with previous fractures, risk factors for osteoporosis, and clinical characteristics in patients with obesity. Subjects and methods: Cross-sectional, retrospective, single-site study including adult patients with body mass index (BMI) ≥ 30 kg/m2 and BMD evaluation between January 2015 and May 2016 selected from a BMD database. Data on demographic characteristics, lifestyle habits, comorbidities, medications, risk factors, previous fractures, and indications for BMD evaluation were collected from the participants' medical records. Results: The study included 619 patients (89.9% women, mean BMI 34.79 ± 4.05 kg/m2). In all, 382 (61.7%), 166 (26.8%), and 71 (11.5%) patients had class 1, 2, and 3 obesity, respectively. The most frequent (29.9%) reason for BMD evaluation was for osteoporosis monitoring. In all, 69.4% of the patients had low BMD. Multivariate analysis showed that age, calcium supplementation, and previous osteoporosis or osteopenia were associated with low BMD, while age, vitamin D supplementation, use of proton pump inhibitors (PPIs), and low BMD were associated with previous fractures (p < 0.05 for all). Conclusions: Among patients with obesity identified from a tertiary hospital database, those with low bone mass and risk factors traditionally associated with fractures had an increased history of fractures. Patients with greater BMI had better bone mass and fewer fractures. These findings indicate that the association between reduced weight, risk factors for osteoporosis, and fractures remained despite the presence of obesity in our population.

Síndrome coronario agudo y densidad mineral ósea en mujeres en etapa de climaterio / Acute Coronary Syndrome and Bone Mineral Density in Women during their Climacteric Stage

Introducción: Se ha descrito una probable asociación entre la presencia de osteopenia/osteoporosis y el riesgo incrementado de cardiopatía isquémica. Objetivo: Determinar la posible asociación entre la presencia de síndrome coronario agudo y la densidad mineral ósea disminuida, así como la relación de ambas condiciones con algunos factores de riesgo cardiovascular y variables de la esfera reproductiva en mujeres en etapa de climaterio. Método: Se realizó un estudio transversal descriptivo con 72 mujeres (34 con síndrome coronario agudo y 38 sin síndrome coronario agudo), que fueron seleccionadas de bases de datos del Instituto de Cardiología y Cirugía Cardiovascular. La densidad mineral ósea se determinó mediante absorciometría dual de rayos X en columna lumbar. Las pruebas Chi cuadrado y U de Mann Whitney permitieron evaluar la posible relación entre variables. Resultados: El 55,9 por ciento de las pacientes con síndrome coronario agudo y el 60,5 por ciento de las mujeres sin síndrome coronario agudo tenían densidad mineral ósea disminuida. En las mujeres con densidad mineral ósea disminuida (n=42): 81 por ciento presentaron obesidad abdominal, 78,6 por ciento dislipoproteinemia, 83,3 por ciento hipertensión arterial y 76,2 por ciento refirieron el antecedente familiar de cardiopatía isquémica. Conclusiones: En las mujeres en etapa de climaterio estudiadas no se demostró asociación entre la presencia de síndrome coronario agudo y la densidad mineral ósea disminuida. Tampoco existió relación entre la presencia de síndrome coronario agudo y la densidad mineral ósea disminuida con factores de riesgo cardiovascular, ni con las variables de la esfera reproductiva(AU)

Introduction: A probable association has been described between the presence of osteopenia/osteoporosis and the increased risk of ischemic heart disease. Objective: To determine the possible association between the presence of acute coronary syndrome and decreased bone mineral density, as well as the relationship of both conditions with some cardiovascular risk factors and variables of the reproductive sphere in women during the climacteric stage. Method: A descriptive and cross-sectional study was carried out with 72 women (34 with acute coronary syndrome and 38 without acute coronary syndrome), who were selected from databases of the Institute of Cardiology and Cardiovascular Surgery. Bone mineral density was determined by dual lumbar spine X-ray absorptiometry. The chi-square and Mann Whitney U tests allowed to evaluate the possible relationship between variables. Results: 55.9 percent of the patients with acute coronary syndrome and 60.5 percent of the women without acute coronary syndrome had decreased bone mineral density. Among women with decreased bone mineral density (n=42), 81 percent had abdominal obesity, 78.6 percent had dyslipoproteinemia, 83.3 percent had arterial hypertension, and 76.2 percent had a family history of ischemic heart disease. Conclusions: In the women in the climacteric stage studied, no association was shown between the presence of acute coronary syndrome and decreased bone mineral density. There was no relationship either between the presence of acute coronary syndrome and decreased bone mineral density with cardiovascular risk factors, or with variables in the reproductive sphere(AU)

Metabolic bone disease in children and adolescent patients with ulcerative colitis

Abstract Objective: Metabolic bone disease concerns a broad spectrum of conditions related to reduced bone density. Metabolic bone disease has been linked to chronic inflammatory diseases, such as ulcerative colitis. This study examines the prevalence of metabolic bone disease in ulcerative colitis patients and explores possible clinical predictors. Method: The authors performed a retrospective study involving children and adolescents with confirmed ulcerative colitis between January 2013 and December 2018. Bone density was evaluated through a dual-energy X-ray absorptiometry scan of the spine and total body. Osteoporosis was defined as a bone mineral density Z-score of <−2 and osteopenia as a Z-score of between −1.0 and −2. Results: A total of 37 patients were included in this analysis, with a mean age of 13.4 ± 3.9 years and a mean duration of illness of 2.1 ± 2.4 years. Using lumbar spine Z-scores and total body Z-scores, osteoporosis and osteopenia were identified by dual-energy X-ray absorptiometry scan measurements in 11 patients (29.7%) and 15 patients (40.5%), and in ten patients (27%) and 13 patients (35%), respectively. Lumbar spine Z-scores were significantly positively associated with male gender (B = 2.02; p = 0.0001), and negatively associated with the presence of extraintestinal manifestations (B = −1.51, p = 0.009) and the use of biologics (B = −1.33, p = 0.004). However, total body Z-scores were positively associated with body mass index Z-scores (B = 0.26, p = 0.004) and duration of illness in years (B = 0.35, p = 0.003). Conclusions: Metabolic bone disease is very common in this cohort of Saudi Arabian children and adolescents with ulcerative colitis and its occurrence appears to increase in female patients who suffer from extraintestinal manifestations.

Risk factors for metabolic bone disease of prematurity in very/extremely low birth weight infants: a multicenter investigation in China / 中国当代儿科杂志

OBJECTIVE@#To investigate the incidence rate and risk factors for metabolic bone disease of prematurity (MBDP) in very low birth weight/extremely low birth weight (VLBW/ELBW) infants.@*METHODS@#The medical data of 61 786 neonates from multiple centers of China between September 1, 2013 and August 31, 2016 were retrospectively investigated, including 504 VLBW/ELBW preterm infants who met the inclusion criteria. Among the 504 infants, 108 infants diagnosed with MBDP were enrolled as the MBDP group and the remaining 396 infants were enrolled as the non-MBDP group. The two groups were compared in terms of general information of mothers and preterm infants, major diseases during hospitalization, nutritional support strategies, and other treatment conditions. The multivariate logistic regression analysis was used to investigate the risk factors for MBDP.@*RESULTS@#The incidence rate of MBDP was 19.4% (88/452) in VLBW preterm infants and 38.5% (20/52) in ELBW preterm infants. The incidence rate of MBDP was 21.7% in preterm infants with a gestational age of < 32 weeks and 45.5% in those with a gestational age of < 28 weeks. The univariate analysis showed that compared with the non-MBDP group, the MBDP group had significantly lower gestational age and birth weight, a significantly longer length of hospital stay, and a significantly higher incidence rate of extrauterine growth retardation (@*CONCLUSIONS@#A lower gestational age, hypocalcemia, extrauterine growth retardation at discharge, and neonatal sepsis may be associated an increased risk of MBDP in VLBW/ELBW preterm infants. It is necessary to strengthen perinatal healthcare, avoid premature delivery, improve the awareness of the prevention and treatment of MBDP among neonatal pediatricians, and adopt positive and reasonable nutrition strategies and comprehensive management measures for preterm infants.

VIH y salud ósea / HIV and bone health

Con el advenimiento de la terapia antirretroviral, el pronóstico y la sobrevida de los pacientes infectados con el virus de la inmunodeficiencia humana (VIH) han cambiado de manera radical, por lo cual en la actualidad se evidencia un aumento en el riesgo de padecer enfermedades no relacionadas con el VIH como, por ejemplo, la osteoporosis. La disminución de la densidad mineral ósea (DMO) se observa en el 40-90% de las personas infectadas por el VIH, con una prevalencia de osteopenia y osteoporosis del 52 y 15%, respectivamente. Esta población de pacientes tiene un mayor riesgo de fracturas (60%) en comparación con personas no infectadas y un riesgo de fracturas vertebrales 2,3 veces mayor que en la población general. El tenofovir fumarato se asoció con un aumento de pérdida renal de fósforo e hiperparatiroidismo secundario. El efavirenz y los inhibidores de proteasas (IP) afectan el metabolismo de la vitamina D; actúan a nivel enzimático aumentando la expresión de la enzima CYP24 que lleva a producción de vitamina D inactiva. El FRAX es una herramienta sencilla y accesible, por lo que su uso está recomendado en pacientes con VIH. Además de las medidas higiénico-dietéticas, actividad física, calcio y vitamina D, el uso de bifosfonatos está indicado en el tratamiento de la osteoporosis en estos pacientes. (AU)

With the advent of antiretroviral therapy, the prognosis and survival of patients infected with the human immunodeficiency virus (HIV) have radically changed, which is why there is now evidence of an increased risk of suffering from diseases not related to HIV such as osteoporosis. The decrease in bone mineral density (BMD) is observed in 40-90% of people infected with HIV, with a prevalence of osteopenia and osteoporosis of 52 and 15%, respectively. This patient population has a 60% higher risk of fractures compared to uninfected people and a risk of vertebral fractures 2.3 times higher than in the general population. Tenofovir fumarate administration is associated with increased renal phosphorus loss and secondary hyperparathyroidism. Efavirenz and protease inhibitors (IP) affect the metabolism of vitamin D, they act at the enzymatic level by increasing the expression of the CYP24 enzyme that leads to the production of inactive vitamin D. The FRAX is a simple and accessible tool, so its use is recommended in patients with HIV and in addition to dietary hygiene measures, physical activity, calcium, and vitamin D, the use of bisphosphonates is indicated in the treatment of osteoporosis in these patients. (AU)

Chronic osteo-articular changes in patients with sickle cell disease

Abstract Background: Sickle cell disease (SCD) is an autosomal recessive genetic disease in which a mutation occurs in the β-globin chain gene, resulting in abnormal hemoglobin levels. In an environment with reduced oxygen concentration, red blood cells change their conformation, resulting in chronic hemolysis and consequent anemia and vaso-occlusive crises with injuries to several organs, with a significant impairment of the osteoarticular system. This study aimed to verify the chronic osteoarticular alterations and their association with clinical and laboratory characteristics of patients with SCD with a more severe phenotype (SS and Sβ0), on a steady-state fasis. Methods: Fifty-five patients were referred to a medical consultation with a specialized assessment of the locomotor system, followed by laboratory tests and radiographic examinations. Results: In total, 74.5% patients had hemoglobinopathy SS; 67.3% were female; and 78.2% were non-whites. The mean patient age was 30.5 years. Most patients (61.8%) reported up to three crises per year, with a predominance of high-intensity pain (65.5%). Radiographic alterations were present in 80% patients. A total of 140 lesions were identified, most which were located in the spine, femur, and shoulders. Most lesions were osteonecrosis and osteoarthritis and were statistically associated with the non-use of hydroxyurea. Conclusions: There was a high prevalence of chronic osteoarticular alterations, which was statistically associated only with the non-regular use of hydroxyurea.(AU)

Hipofosfatasemia crónica persistente de causa no determinada y su repercusión músculo-esquelética / Persistent hypophosphatasemia and its musculoskeletal repercussion

La fosfatasa alcalina baja o hipofosfatasemia, ya sea debida a causas genéticas (hipofosfatasia) o secundarias, presenta correlato clínico. Nuestro objetivo es estimar la prevalencia de hipofosfatasemia crónica persistente y describir sus hallazgos osteometabólicos. Se realizó una búsqueda electrónica de afiliados adultos al Hospital Italiano de Buenos Aires, entre 2013 y 2017, con al menos 2 determinaciones de fosfatasa alcalina igual a 30 UI/l o menor y ninguna mayor de 30 UI/l (rango de referencia 30-100 UI/l). Se excluyeron aquellos con causas secundarias diagnosticadas y se analizaron los correlatos clínico y bioquímico. Se detectó hipofosfatasemia crónica persistente en 78 de 105.925, 0,07% (0,06-0,09) de los afiliados. Solo uno fue excluido por tener causa secundaria. Eran 61,1% mujeres de 44 (34-56) años, fosfatasa alcalina 24 (20-27) UI/L, fosfatemia 4,1 (3,8-4,6) mg/dl. Se observaron osteoartritis, calcificaciones vasculares y fracturas, menos frecuentemente litiasis renal, calcificación del ligamento longitudinal común anterior, pérdida dental y convulsiones. El 63,6% tenían al menos una de las características clínico-radiológicas evaluadas, pero en solo 5,2% fue mencionado el diagnóstico de hipofosfatasemia en la historia clínica. La densitometría evidenció algún grado de afección (osteopenia u osteoporosis) en 76,2%. Se constataron 19 fracturas, con predominio en radio. La prevalencia de hipofosfatasemia fue similar a lo previamente reportado. El reconocimiento fue bajo; sin embargo, se observaron variadas manifestaciones músculo-esqueléticas, similares a las descriptas en la hipofosfatasia del adulto, por lo cual ­ante una hipofosfatasemia sin causa secundaria­ se sugiere considerar este diagnóstico. (AU)

Low alkaline phosphatase (ALP) or hypophosphatasemia either due to genetic (hypophosphatasia) or secondary causes, presents a clinical correlate. Our objectives are to estimate the prevalence of persistent hypophosphatasemia and to describe the clinical findings. We performed a search using the electronic medical records of the members of the Hospital Italiano de Buenos Aires health care system, between 2013 and 2017. Adult members with ≥ 2 ALP ≤ 30 IU/l, no ALP >30 IU/l (normal range 30-100 UI/l) and without diagnosed secondary causes were analyzed. Persistent hypophosphatasemia was detected in 78 of 105.925, 0.07% (0.06-0.09) of members. Only one was excluded due to a secondary cause, 61.1% were women, 44 (34-56) year-old, ALP 24 (20-27) IU/l and phosphatemia 4.1 (3.8-4.6) mg/dl. Osteoarthritis, vascular calcifications and fractures were detected, and nephrolithiasis, DISH (Diffuse idiopathic skeletal hyperostosis), tooth loss, and seizures were less frequently observed. At least one of the mentioned characteristics were present in 63.6 %, but only 5.2% had hypophosphatasemia registered in their clinical record. Densitometry showed osteopenia or osteoporosis in 76.2%. There were 19 fractures, most of them in radius. The prevalence of hypophosphatasemia was similar to what has been previously reported. Hypophosphatasemia finding in medical records was low, but far from being asymptomatic, clinical manifestations were observed. In the presence of hypophosphatasemia without a secondary cause, adult hypophosphatasia should be uspected. (AU)

Renal osteodystrophy and clinical outcomes: data from the Brazilian Registry of Bone Biopsies - REBRABO / Osteodistrofia renal e desfechos clínicos: dados do Registro Brasileiro de Biópsias Ósseas - REBRABO

ABSTRACT Introduction: Mineral and bone disorders (MBD) are major complications of chronic kidney disease (CKD)-related adverse outcomes. The Brazilian Registry of Bone Biopsy (REBRABO) is an electronic database that includes renal osteodystrophy (RO) data. We aimed to describe the epidemiological profile of RO in a sample of CKD-MBD Brazilian patients and understand its relationship with outcomes. Methods: Between August 2015 and March 2018, 260 CKD-MBD stage 3-5D patients who underwent bone biopsy were followed for 12 to 30 months. Clinical-demographic, laboratory, and histological data were analyzed. Bone fractures, hospitalizations, and death were considered the primary outcomes. Results: Osteitis fibrosa, mixed uremic osteodystrophy, adynamic bone disease, osteomalacia, osteoporosis, and aluminum (Al) accumulation were detected in 85, 43, 27, 10, 77, and 65 patients, respectively. The logistic regression showed that dialysis vintage was an independent predictor of osteoporosis (OR: 1.005; CI: 1.001-1.010; p = 0.01). The multivariate logistic regression revealed that hemodialysis treatment (OR: 11.24; CI: 1.227-100; p = 0.03), previous parathyroidectomy (OR: 4.97; CI: 1.422-17.241; p = 0.01), and female gender (OR: 2.88; CI: 1.080-7.679; p = 0.03) were independent predictors of Al accumulation; 115 patients were followed for 21 ± 5 months. There were 56 hospitalizations, 14 deaths, and 7 fractures during follow-up. The COX regression revealed that none of the variable related to the RO/turnover, mineralization and volume (TMV) classification was an independent predictor of the outcomes. Conclusion: Hospitalization or death was not influenced by the type of RO, Al accumulation, or TMV classification. An elevated prevalence of osteoporosis and Al accumulation was detected.

RESUMO Introdução: Os distúrbios minerais e ósseos (DMO) são importantes complicações da doença renal crônica (DRC) associadas à desfechos adversos. O Registro Brasileiro de Biópsia Óssea (REBRABO) é um banco de dados eletrônico que inclui dados sobre osteodistrofia renal (OR). Nosso objetivo foi descrever o perfil epidemiológico da OR em uma amostra de pacientes brasileiros com DMO-DRC e entender sua associação com os desfechos. Métodos: Entre agosto de 2015 e março de 2018, 260 pacientes com DMO-DRC estágio 3-5D submetidos à biópsia óssea foram acompanhados por 12 a 30 meses. Dados clínico-demográficos, laboratoriais e histológicos foram analisados. Fraturas ósseas, hospitalizações e óbito foram considerados como desfechos primários. Resultados: Osteíte fibrosa, osteodistrofia urêmica mista, doença óssea adinâmica, osteomalácia, osteoporose e acúmulo de alumínio (Al) foram detectados em 85, 43, 27, 10, 77 e 65 pacientes, respectivamente. A regressão logística mostrou que o tempo em diálise foi um preditor independente de osteoporose (OR: 1.005; IC: 1.001-1.010; p = 0,01). A regressão logística multivariada revelou que o tratamento hemodialítico (OR: 11,24; IC: 1,227-100; p = 0,03), paratireoidectomia prévia (OR: 4,97; IC: 1,422-17,241; p = 0,01) e sexo feminino (OR: 2,88; IC: 1,080-7,679; p = 0,03) foram preditores independentes de acúmulo de Al; 115 pacientes foram acompanhados por 21 ± 5 meses. Houve 56 internações, 14 óbitos e 7 fraturas durante o seguimento. A regressão COX revelou que nenhuma das variáveis relacionadas ao tipo de OR/remodelação-mineralização-volume (classificação TMV) foi um preditor independente de desfechos. Conclusão: A hospitalização ou óbito não foram influenciadas pelo tipo de OR, acúmulo de Al ou classificação de TMV. Foi detectada uma prevalência elevada de osteoporose e acúmulo de Al.

Hiperkalemia postoperatoria en síndrome de hueso hambriento post-paratiroidectomía por hiperparatiroidismo secundario en enfermedad renal crónica terminal / Hyperkalemia-associated hungry bone syndrome post-parathyroidectomy in end-stage denal disease

Introducción: El hiperparatiroidismo secundario (HPTS) es una complicación de la enfermedad renal crónica terminal (ERCT). A pesar de nuevas terapias médicas como calcimiméticos, en HPTS refractarios la paratiroidectomía (PTX) continúa siendo necesaria. Una complicación frecuente en estos pacientes posterior a la PTX es el síndrome de hueso hambriento (SHH), caracterizado por una profunda y prolongada hipocalcemia asociada a hipofosfatemia, secundaria a un excesivo aumento de su captación ósea. Una complicación menos descrita, pero con consecuencias graves e incluso fatales, es la hiperkalemia. El propósito de este trabajo consiste en enfatizar el riesgo de hiperkalemia por SHH a partir de un caso clínico, señalar los mecanismos fisiopatológicos, factores de riesgo y consideraciones terapéuticas. Caso clínico: Mujer de 35 años, con ERCT de causa desconocida, HPTS refractario con PTX total e implante de glándulas en antebrazo hace 9 años. Ingresa por recurrencia de HPTS. Cintigrama MIBI SPECT/CT® evidenció implante hiperfuncionante, indicándose PTX del injerto. Exámenes preoperatorios: calcemia 8.6 mg/dL, fosfatasas alcalinas 1115 UI/L (VN <100), PTH intacta (PTHi) 3509 pg/ml y kalemia 4.8 mEq/L. Biopsia: hiperplasia paratiroidea nodular. En postoperatorio inmediato presentó hiperkalemia de 7.1 mEq/L con cambios electrocardiográficos, requiriendo hemodiálisis de urgencia. Posteriormente desarrolló hipocalcemia, hipofosfatemia e hipomagnesemia, de difícil control. Discusión: El SHH post HPTS puede coexistir con hiperkalemia postoperatoria inmediata grave, incluso fatal si no se identifica y corrige a tiempo. El mecanismo fisiopatológico aún no está bien dilucidado. Varios factores pudieran intervenir, incluyendo aumento del metabolismo celular, traumatismo tisular, fármacos anestésicos, fluidos perioperatorios y flujo de iones transmembrana. El nivel de potasio previo a la cirugía, menor edad, género masculino, tiempo entre la última hemodiálisis y la cirugía, y duración de la PTX, son factores de riesgo para hiperkalemia postoperatoria. El conocimiento de esta grave complicación permitirá estar preparado para monitorizar y eventualmente tratar.

Introduction: Secondary Hyperparathyroidism (SHPT) is a complication of End-Stage Renal Disease (ESRD). Although new medical therapies (i.e.calcimimetics,) parathyroidectomy (PTX) continues to be necessary in refractory cases. A well-known complication after PTX is an entity called Hungry Bone Syndrome (HBS), characterized by deep and prolonged hypocalcemia associated with hypophosphatemia, secondary to an excessive increase in bone formation. A less reported complication, but with severe or even fatal consequences, is hyperkalemia. The purpose of this work consists of emphasizing the risk of hyperkalemia in HBS, reporting a clinical case that points out the physiopathological mechanisms, risk factors, and therapeutic considerations. Clinical case: 35-year-old woman with ESRD of unknown cause with refractory SHPT with total PTX and forearm gland grafts nine years ago. She presented SHPT recurrency. MIBI SPECT/CT® scan showed a hyperfunctioning implant, indicating graft PTX. Preoperative tests: calcemia 8.6 mg/dL, phosphatemia 7.3 mg/dL, alkaline phosphatases 1115 UI/L (VN<100), intact PTH (iPTH) 3509 pg/ml and kalemia 4.8 mEq/L. Biopsy: parathyroid nodular hyperplasia. In the immediate postoperative period, she presented hyperkalemia at 7.1 mEq/L with electrocardiographic changes, requiring emergency hemodialysis. Later she developed hypocalcemia, hypophosphatemia, and hypomagnesemia of difficult control. Discussion: HBS post PTX can coexist with severe immediate postoperative hyperkalemia, which can be even fatal if not detected and corrected. The physiopathological mechanism is still not entirely elucidated. Various factors could interfere, including an increase in cell metabolism, tissue traumatism, anesthetic drugs, intraoperative fluids, and transmembrane ion flow. Preoperative potassium levels, younger age, male gender, the time elapsed between last hemodialysis and surgery, and duration of PTX are risk factors for post-surgical hyperkalemia. Knowing this severe complication will allow the medical team to be prepared for monitoring and eventually treating it.

Uso de bifosfonatos en pacientes con osteopenia / Biphosphonates in patients with osteopenia

La osteopenia, una disminución de la densidad mineral ósea de menor severidad que la osteoporosis, definida por valores de T-score entre -1,0 y -2,5 en la densitometría ósea , podría asociarse con un mayor riesgo de fracturas. Motivado por el pedido de una paciente con osteopenia que solicita a su médico algún medicamento que le ayude a disminuir su riesgo de fracturas, el autor se pregunta si los bifosfonatos podrían ser beneficiosos para las pacientes con este factor de riesgo. Luego de realizar una búsqueda bibliográfica y seleccionar la evidencia más reciente y de mejor calidad, se concluye que estos fármacos podrían ser útiles para prevenir fracturas en mujeres mayores de 65 años con elevado riesgo de fractura,independientemente del resultado de la densitometría. (AU)

Osteopenia, a minor decrease in bone mineral density, defined by T-score values between -1.0 and -2.5 in a bone densitometry, is associated with an increased risk of fractures. Moved by the request of a patient with osteopenia who asks her doctor for any medication that may help her reduce his risk of fractures, the author wonders if bisphosphonates could be beneficial for patients with this condition. After conducting a bibliographic search and selecting the most recent and best quality evidence, he concluded that these drugs could be useful to prevent fractures in women older than 65 years with ahigh risk of fracture, regardless of densitometry results. (AU)

Cuidados médicos en EII: más allá de la terapia convencional / Medical care in IBD: more than conventional therapy

The management of Inflammatory Bowel Disease has progressed over the years largely due to better therapeutic options. These current management is guided by the primary goal in achieving clinical and endoscopic remission (deep remission), thus improving the quality of life of patients. In order to achieve these objectives however, there are risks associated which must always be considered. It is important to recognize that IBD patients are at risk of infection and neoplastic lesions for the natural history of the disease or the therapies that we used. Prevention of possible complications must be carried out. Options in therapeutic management not only include pharmacological therapy, but also include an adequate nutritional setting and an optimal correction of nutritional deficits. These alternative nutritional strategies can and should be considered as an effective therapeutic strategy aimed at improving the quality of life of IBD patients.

El manejo de la enfermedad inflamatoria intestinal ha progresado con el paso de los años dado a mayores opciones terapéuticas. El manejo actual se guía por objetivos para lograr remisión clínica y endoscópica (remisión profunda) mejorando así la calidad de vida de estos pacientes. Sin embargo, para lograr estos objetivos, se debe considerar siempre los riesgos asociados a las nuevas terapias. Es importante reconocer que los pacientes con EII son personas en riesgo tanto de infecciones como de lesiones neoplásicas por la historia natural de la enfermedad y/o por las terapias utilizadas, por lo tanto, la prevención de posibles complicaciones debe ser realizada en forma periódica. Por otro parte, el manejo terapéutico, no solo incluye la terapia farmacológica, sino también una adecuada optimización nutricional y una adecuada corrección de los déficit nutricionales secundarios. En este mismo sentido terapias alternativas, pueden ser consideradas como estrategia terapéuticas complementarias destinadas a mejorar la calidad de vida de estos pacientes.

De la osteología a la osteomiología: tres décadas de aportes originales continuos al análisis biomecánico osteomuscular / From osteology to osteo-myology: three decades of continuous, original contributions to musculoskeletal biomechanical analysis

En consonancia con la orientación tradicional de nuestras investigaciones, la Osteología está incorporando progresivamente el análisis estructural-biomecánico óseo y las interacciones músculo-esqueléticas. En este artículo se sintetizan los aportes originales del CEMFoC a la Osteología moderna en el terreno biomecánico en forma didáctica, para que el lector aprecie sus posibles aplicaciones clínicas. Los hallazgos aportaron evidencias sucesivas en apoyo de dos proposiciones fundamentales: a) los huesos deben interpretarse como estructuras resistivas, biológicamente servocontroladas ("Los huesos tienden siempre a mantener un factor de seguridad que permite al cuerpo trabajar normalmente sin fracturarse" ­ Paradigma de Utah) y b) los huesos interactúan con su entorno mecánico, determinado principalmente por las contracciones musculares, en forma subordinada al entorno metabólico ("Los huesos son lo que los músculos quieren que sean, siempre que las hormonas lo permitan"). Los avances producidos se refieren, tanto cronológica como didácticamente, al conocimiento osteológico en general y al desarrollo de recursos novedosos para el diagnóstico no invasivo de fragilidad ósea, para distinguir entre osteopenias y osteoporosis, y para discriminar entre sus etiologías 'mecánica' y 'sistémica'. Finalmente, el nuevo conocimiento se integra en la proposición de un algoritmo diagnóstico para osteopenias y osteoporosis. El espíritu general de la presentación destaca que la evaluación osteomuscular dinámicamente integrada genera un nuevo espacio de análisis personalizado de los pacientes para la atención de cualquier osteopatía fragilizante con criterio biomecánico. (AU)

In consonance with the traditional spirit of our studies, skeletal research is being progressively focused on the structural-biomechanical analysis of bone and the muscle-bone interactions. In this article, the CEMFoC's members summarize their original findings in bone biomechanics and their potential clinical applications. These findings provided evidence supporting two fundamental hypotheses, namely, A. bones constitute resistive structures, which are biologically servo-controlled ('Bones tend to maintain a safety factor which allows the body to function normally avoiding fractures' ­ the 'Utah paradigm'), and B. the interactions of bones with their mechanical environment mainly are determined by the contraction of local muscles - 'bone-muscle units'), and are subordinated to the control of the metabolic environment ('Bones are what muscles wish them to be, provided that hormones allow for it'). The achievements in the field are presented in a chronological and didactical sequence concerning the general knowledge in Osteology and the development of novel resources for non-invasive diagnosis of bone fragility, aiming to distinguish between osteopenias and osteoporosis and the 'mechanical' and 'metabolic' etiology of these conditions. Finally, the integrated new knowledge is presented as supporting for a proposed diagnostic algorithm for osteopenias and osteoporosis. In general terms, the article highlights the dynamic evaluation of the musculoskeletal system as a whole, opening a new diagnostic field for a personalized evaluation of the patients affected by a boneweakening disease, based on functional and biomechanical criteria. (AU)

Prevalencia de causas secundarias de baja masa ósea en una población de mujeres premenopáusicas / Prevalence of secondary causes in a population of premenopausal women with low bone mass

La osteoporosis es un trastorno común en las mujeres posmenopáusicas; sin embargo, también puede afectar a hombres y mujeres jóvenes premenopáusicas. El objetivo del presente trabajo fue evaluar la prevalencia de causas secundarias de baja masa ósea en un grupo de mujeres premenopáusicas que consultaron en una Institución especializada en Osteología. Material y métodos: se realizó un estudio retrospectivo, de corte transversal, descriptivo y observacional. Se analizaron las historias clínicas de 88 pacientes que consultaron por baja masa ósea durante un período de 19 meses, con la finalidad de encontrar posibles causas secundarias. A su vez, se definió como pacientes con diagnóstico de baja masa ósea idiopática aquellas en las cuales no se encontró ninguna causa secundaria de pérdida ósea. Resultados: de las 88 mujeres evaluadas, el 48,9% presentaba al menos una causa secundaria para baja masa ósea (amenorrea secundaria, hipercalciuria, tratamiento con glucorticoides, hipovitaminosis D y enfermedad celíaca) y el 51,1% fueron consideradas idiopáticas. Conclusiones: es esencial evaluar exhaustivamente a las mujeres premenopáusicas con baja masa ósea a fin de descartar posibles causas secundarias y tomar las medidas preventivas necesarias para mejorar esa condición. (AU)

Objective: osteoporosis is a common disorder in postmenopausal women, however it can also affect men and premenopausal young women. The purpose of this study was to evaluate the prevalence of secondary causes of low bone mass in premenopausal women that consulted physicians in an institution specialized in osteology for a period of 19 months. Material and methods: this is a retrospective, transversal, descriptive and observational study. The clinical history of 88 patients who consulted a physician due to low bone mass for a period of 19 months in an institution specialized in osteology. Were analyzed the patient's clinical history in order to find secondary causes. We define as suffering Low Bone Mass those patients who did not have secondary causes. Results: of the 88 women tested, 48,9% had one or more secondary causes or risks factors for low bone mass (secondary amenorrea, hypercalciuria, treatment with glucocorticoids, hypovitamiosis D and celiac disease) and 51,1% patients were considered idiopathic. Conclusions: we conclude that it is essential to exhaustively search for secondary causes of low bone mass in premenopausal women, due to the high prevalence of secondary osteoporosis in this population. (AU)

Hepatic Osteodystrophy: The Mechanism of Bone Loss in Hepatocellular Disease and the Effects of Pamidronate Treatment

OBJECTIVES: The present study was designed to evaluate the bone phenotypes and mechanisms involved in bone disorders associated with hepatic osteodystrophy. Hepatocellular disease was induced by carbon tetrachloride (CCl4). In addition, the effects of disodium pamidronate on bone tissue were evaluated. METHODS: The study included 4 groups of 15 mice: a) C = mice subjected to vehicle injections; b) C+P = mice subjected to vehicle and pamidronate injections; c) CCl4+V = mice subjected to CCl4 and vehicle injections; and d) CCl4+P = mice subjected to CCl4 and pamidronate injections. CCl4 or vehicle was administered for 8 weeks, while pamidronate or vehicle was injected at the end of the fourth week. Bone histomorphometry and biomechanical analysis were performed in tibiae, while femora were used for micro-computed tomography and gene expression. RESULTS: CCl4 mice exhibited decreased bone volume/trabecular volume and trabecular numbers, as well as increased trabecular separation, as determined by bone histomorphometry and micro-computed tomography, but these changes were not detected in the group treated with pamidronate. CCl4 mice showed increased numbers of osteoclasts and resorption surface. High serum levels of receptor activator of nuclear factor-κB ligand and the increased expression of tartrate-resistant acid phosphatase in the bones of CCl4 mice supported the enhancement of bone resorption in these mice. CONCLUSION: Taken together, these results suggest that bone resorption is the main mechanism of bone loss in chronic hepatocellular disease in mice.

Alert for bone alterations and low serum concentrations of vitamin D in patients with intestinal inflammatory disease / Alerta para alterações ósseas e baixas concentrações séricas de vitamina D em pacientes com doença inflamatória intestinal

Summary Background: Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are characterized by chronic inflammation of the intestine that can reduce the absorption of nutrients such as vitamin D and calcium. Objective: To investigate bone alterations and serum levels of vitamin D in patients with IBD. Method: This was a cross-sectional study based on a review of medical records of patients from a private office in Curitiba, PR, Brazil. Serum levels of vitamin D and bone densitometry were measured at diagnosis of IBD. A total of 105 patients were included; 38 (58.4%) with CD; 27 (41.6%) with UC and 40 with irritable bowel syndrome (IBS) as comparison group. Results: When compared to patients with UC, CD patients showed a higher prevalence of bone alterations, being 15.8% with osteoporosis and 36.8% with osteopenia. In UC, bone alterations occurred in 29.6% of cases, 3.7% with osteoporosis and 25.9% with osteopenia. As for vitamin D levels, among CD patients, 10.5% had vitamin deficiency, 65.8% insufficiency and 23.7% were sufficient. In UC, 7.4% of cases had deficiency, 74.1% insufficiency and 18.5% had sufficient serum levels of vitamin D. In the group with IBS, deficiency was observed in 17.5% of cases, insufficiency in 55% and sufficiency in 27.5% of them. There was no significant difference between groups. Conclusion: IBD patients have a high prevalence of bone changes, especially those with CD. Serum levels of vitamin D are below the recommended in all the evaluated groups.

Resumo Introdução: A doença inflamatória intestinal (DII), como a doença de Crohn (DC) e a retocolite ulcerativa (RU), caracterizam-se pela inflamação crônica no intestino, que pode reduzir a absorção de vitamina D e cálcio. Objetivo: Investigar as alterações ósseas presentes em pacientes com DII e as dosagens séricas de vitamina D. Método: Estudo transversal analítico baseado na revisão de prontuários de pacientes com DII de um consultório privado de Curitiba, PR. Em todos os pacientes, foram dosadas as concentrações séricas de vitamina D e foi feita a densitometria óssea. Cento e cinco pacientes foram incluídos no estudo, dos quais 38 (58,4%) foram diagnosticados com DC, 27 (41.6%) com RU e 40 com síndrome do intestino irritável (SII) como grupo de comparação. Resultados: Quando comparados com pacientes com RU, os pacientes com DC apresentaram maior prevalência de alterações ósseas, sendo 15,8% com osteoporose e 36,8% com osteopenia. Na RU, as alterações ósseas ocorreram em 29,6% dos casos, 3,7% com osteoporose e 25,9% com osteopenia. Em relação às dosagens de vitamina D, dentre os pacientes com DC, 10,5% apresentavam deficiência, 65,8%, insuficiência e 23,7%, suficiência. Na RU, 7,4% dos casos tinham deficiência, 74,1%, insuficiência e 18,5%, suficiência. No grupo com SII, observaram-se deficiência em 17,5%, insuficiência em 55% e suficiência em 27,5%. Não foi observada diferença significativa entre os grupos. Conclusão: Pacientes com DII apresentaram alta prevalência de alterações ósseas, principalmente aqueles com DC. As concentrações séricas de vitamina D estão abaixo do recomendado em todos os grupos avaliados.

Factores de riesgo y marcadores bioquímicos de la enfermedad metabólica ósea del recién nacido prematuro / Risk factors and biochemical markers in metabolic bone disease of premature newborns

Introducción: La enfermedad metabólica ósea (EMO) del recién nacido prematuro (RNPT) es una complicación de origen multifactorial, que ha ido en aumento, consecuencia de la disminución progresiva de la mortalidad. El objetivo del estudio fue analizar los factores de riesgo (FR) pre y postnatales relacionados con la EMO severa y sus marcadores analíticos. Pacientes y Métodos: Estudio retrospectivo observacional, descriptivo y analítico, que incluyó RNPT nacidos con menos de 32 semanas y/o peso menor de 1.500 g entre enero de 2012 y diciembre de 2014. Se analizó la muestra en función del desarrollo de EMO severa. Resultados: 139 pacientes, con 25(OH)D3 media de 70,68 ± 25,20 nmol/l, mayor en los nacidos en primavera-verano que en otoño-invierno (80,94 ± 25,33 vs 61,13±21,07; p = 0,000). Los pacientes con EMO severa presentaron valores de 25(OH)D3 similares al resto de pacientes (65,61 ± 26,49 vs 72,07 ± 24,89; p = 0,283), y superiores de fosfatasa alcalina (FA) (1314,19 ± 506,67 vs 476,56 ± 188,85; p = 0,000). Mediante curva ROC se calculó un punto de corte de FA de 796,5 IU/l (S 95,2%, E 92,4%). Los FR más asociados al desarrollo de EMO severa fueron el crecimiento intrauterino restringido, el peso al nacimiento y la duración de ventiloterapia y nutrición parenteral. Conclusiones: Las cifras de FA son las que mejor se relacionan con el desarrollo de EMO severa. El riesgo de ésta aumenta a mayor número de factores de riesgo y menores cifras de vitamina D3. Niveles de 25(OH)D3 por encima de 70 nmol/l parecen proteger del desarrollo de EMO, incluso en pacientes con múltiples factores de riesgo.

Background: Metabolic bone disease (MBD) of prematurity is a complication of multifactorial aetiology, which has been increasing, due to progressive decrease in mortality of preterm newborns. The aim of the study was to analyze risk factors of severe MBD and its analytical markers. Patients and Method: Retrospective study involving preterm infants less than 32 weeks gestational age and/or weight less tan 1,500 g born between january 2012 and december 2014. Comparison was made according to the presence of severe MBD. Results: 139 patients were recruited. Mean value of 25(OH)D3 was 70.68 ± 25.20 nmol/L, being higher in patients born in spring-summer than in autumn-winter (80.94 ± 25.33 vs 61.13 ± 21.07; p = 0.000). Levels of 25(OH)D3 were similar in patients with severe MBD compared with the rest of patients (65.61 ± 26.49 vs 72.07 ± 24.89, P = 0.283). Higher levels of alkaline phosphatase (AP, IU/L ) (1314.19 ± 506.67 vs 476.56 ± 188.85; p = 0.000) were found in these patients. Cutoff point of AP 796.5 IU/L (S 95.2%, specificity 92.4%) was calculated by ROC curve. The risk factors most associated to severe EMO were restricted fetal growth, birth weight, duration of ventilation therapy and parenteral nutrition. Conclusions: AP levels were the best marker of severe MBD development. EMO risk increases with the number of risk factors and lower levels of 25(OH)D3. Levels of 25(OH)D3 higher than 70nmol/L appear to protect from the development of severe MBD, even in patients with multiple risk factors.