Diagnostic challenges in hypophosphatasia in adult patients / Desafios do diagnóstico da hipofosfatasia em adultos

Introdução: Hipofosfatasia é um distúrbio metabólico que afeta a mineralização óssea e dentária, causada por mutações no gene ALPL, levando à deficiência enzimática da fosfatase alcalina tecido não-específica. A forma adulta caracteriza-se por fraturas atípicas do fêmur, osteomalácia, osteoporose, grave osteoartropatia, condrocalcinose e artralgia. Objetivo: Demonstrar desafios diagnósticos relacionados à hipofosfatasia através do relato de dois casos. Paciente 1: feminino, 59 anos, encaminhada para avaliação clínica devido às fraturas patológicas de difícil consolidação e osteoporose generalizada de causa genética. Relata perda dentária precoce da arcada superior, fraturas na coluna, em ombro esquerdo e no fêmur. Atualmente, queixa-se de dor crônica intensa, com uso de múltiplos medicamentos. Achados clínicos, laboratoriais e radiológicos foram compatíveis com o diagnóstico de hipofosfatasia. Paciente 2: masculino, 31 anos, filho da paciente 1, encaminhado para avaliação clínica por fratura patológica precoce em fêmur esquerdo e osteoporose não esclarecida. Atualmente relata dor e claudicação importante em membro inferior esquerdo, associado à lombalgia crônica. Confirmação do diagnóstico de hipofosfatasia por exames laboratoriais e radiológicos e sequenciamento do gene ALPL, aliados ao diagnóstico da sua genitora. Discussão: Hipofosfatasia é uma doença rara de herança autossômica dominante e recessiva. Pacientes acometidos apresentam fraturas constantes, densidade mineral óssea baixa, cicatrização óssea deficitária. É comum a hipofosfatasia ser diagnosticada erroneamente como osteopenia e/ou osteoporose primária, acarretando prejuízos ao paciente. Ressalta-se a importância da história clínica completa e dos antecedentes familiares a fim de se obter um diagnóstico precoce, garantindo, por sua vez, o adequado acompanhamento e manejo terapêutico (AU)

Introduction: hypophosphatasia is a metabolic disorder affecting bone and tooth mineralization, caused by mutations in the ALPL gene leading to enzymatic deficiency of tissue non-specific alkaline phosphatase. The adult form is characterized by atypical femur fractures, osteomalacia, osteoporosis, severe osteoarthropathy, chondrocalcinosis, and arthralgia. Objective: to demonstrate diagnostic challenges related to hypophosphatasia through the report of two cases. Patient 1: female, 59 years old, referred for clinical evaluation due to pathological fractures of difficult consolidation and generalized osteoporosis of genetic cause. She reports early tooth loss in the upper arch, fractures in the spine, left shoulder and femur. Currently, he complains of severe chronic pain, with use of multiple medications. Clinical, laboratory, and radiological findings were compatible with the diagnosis of hypophosphatasia. Patient 2:male, 31 years old, son of patient 1, referred for clinical evaluation due to an early pathological fracture in the left femur and unclear osteoporosis. He currently reports pain and significant claudication in the left lower limb, associated with chronic low back pain. Confirmation of the diagnosis of hypophasatasia by laboratory and radiological tests and sequencing of the ALPL gene combined with the diagnosis of his mother. Discussion: hypophosphatasia is a rare disease of autosomal dominant and recessive inheritance. Affected patients have constant fractures, low bone mineral density, and impaired bone healing. It is common for hypophosphatasia to be misdiagnosed as osteopenia and/or primary osteoporosis, which can be harmful to the patient. The importance of a complete clinical history and family history is emphasized in order to obtain an early diagnosis, ensuring adequate follow-up and therapeutic management (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.

Osteosarcopenia: del envejecimiento de la unidad óseo-muscular a la enfermedad / Osteosarcopenia: from muscle-bone unit aging to disease

Aunque la masa muscular y la ósea tienen igual origen embriológico, desarrollo y función, por lo que constituyen la unidad hueso-músculo, las enfermedades asociadas al envejecimiento de esta unidad se consideran de manera independiente. Sin embargo, en los últimos años se evidencia el efecto aditivo nocivo que genera la sarcopenia y la osteopenia/osteoporosis en la calidad de vida y la salud del adulto mayor y aparece el concepto de osteosarcopenia. Entre los adultos mayores se reporta la disminución progresiva de la masa y la fuerza musculares, y las caídas accidentales en el hogar (probables por fragilidad) que están entre las principales causas de muerte, lo que sugiere que un grupo de estos adultos mayores pudieran tener osteosarcopenia. Por ello se requiere desarrollar capacidades para su prevención. Se realiza una revisión narrativa para actualizar aspectos del envejecimiento de la unidad óseo-muscular, la importancia de la osteosarcopenia, sus criterios diagnósticos y opciones terapéuticas. Se estudiaron artículos completos, en idioma inglés y español, obtenidos de las bases de datos Pubmed, Scielo Regional y Google Scholar. La infiltración grasa de la unidad músculo-hueso es el evento más importante del envejecimiento, pero no existe uniformidad en el diagnóstico de la sarcopenia. Hasta el presente un aporte proteico de calcio y vitamina D, unido a ejercicios de fuerza, son las principales opciones terapéuticas. No se dispone de fármacos que actúen al unísono sobre las dos entidades que conforman la osteosarcopenia(AU)

Muscle and bone mass have the same embryological origin, development and function constituting the bone-muscle unit. However, the diseases associated with aging of this unit are considered independently. In recent years, the additive effect of sarcopenia and osteopenia / osteoporosis on the quality of life and health of the elderly has been revealed, and thus the concept of Osteosarcopenia emerged. In older adults, reporting a progressive decrease in muscle mass and strength. Along with the above, accidental falls at home (by fragility?) are among its main causes of death, suggesting that a group of these aging people may have undiagnosed Osteosarcopenia. To develop capacities for its prevention the objective of this narrative revision are update aspects related to the aging of muscle. Bone unit and diagnostic criteria and therapeutic options for Osteosarcopenia. Exhaustive review of complete articles, in English and Spanish, downloaded manually and published between 2010 and 2019, obtained from the Pubmed, Scielo Regional and Google Scholar databases. the fatty infiltration of the muscle-bone unit It is the most important event of aging, there is no uniformity in the diagnosis of sarcopenia and adequate protein intake, calcium and D vitamin and strength exercises are principal therapeutic options. There are no drugs with on both entities(AU)

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.

Intercellular mediators in bone remodeling regulation in the experimental renal pathology / Mediadores intercelulares de la regulación de la remodelación ósea en un modelo experimental de patología renal

Bone metabolism disorders are characterized by an imbalance of bone resorption and formation in the bone remodeling process. Glucocorticoids that are used to treat kidney diseases exacerbate these disorders. P-selectin and galectin-3 are molecules involved in the sclerotic process in kidney, whereas bone resorption is regulated by the interaction between the nuclear factor activator kappa b receptor (RANK), its ligand (RANKL) and the RANKL decoy receptor osteoprotegerin (OPG). The aim of this study was to investigate the cellular and molecular mechanisms of disruption of bone remodeling regulation processes, reflected by intercellular mediators (RANKL, OPG, P-selectin and galectin-3) in chronic kidney disease experimental model treated with glucocorticoids. Rats were divided into four groups of 10 animals each. The first group, the control group, included intact animals. The second group consisted of rats with impaired bone remodeling resulting from chronic kidney disease (experimental group (CKD). The third group was a group of animals with impaired bone remodeling due to exposure to glucocorticoids (experimental group (GCs)). The fourth group consisted of rats with impaired bone remodeling in chronic kidney disease, followed by exposure to glucocorticoids (experimental group (CKD + GCs)). The effects of CKD and glucocorticoid were evaluated biochemically, histologically and by measuring bone density. An enzymelinked immunoassay was used to measure intercellular mediator levels in the serum. The bone density in the experimental groups was reduced compared to the control group. RANKL levels in animals of three experimental groups were higher than in intact animals. Serum levels of OPG were higher in CKD and GCs groups than in intact animals. At the same time, in the animals' blood serum of the CKD + GCs group, the levels of OPG were lower, than those in animals from the control group. The levels of galectin-3 in the serum of the experimental groups GCs and CKD + GCs were lower than in intact animals. The serum levels of galectin-3 in animals of the CKD group were higher than those in animals from the control group. The levels of P-selectin were lower in the serum of the GCs group than in intact animals. At the same time, the levels of P-selectin were higher in the CKD and CKD + GCs groups, than those in animals from the control group. In conclusion, the study of the complex system of bone remodeling regulation, which includes many factors and their interactions, may lead to the development of new methods for treating patients with chronic kidney disease in order to prevent osteoporosis in the future. (AU)

Las enfermedades metabólicas óseas se caracterizan por un desequilibrio en el proceso de remodelación ósea en los que participan mediadores tales como receptor del activador del factor nuclear- kappa- b (RANK), su ligando (RANKL) y la osteoprotegerina (OPG). Los glucocorticoides, recuentemente empleados en el tratamiento de la enfermedad renal crónica, exacerban este desequilibrio. En la enfermedad esclerótica renal, las moléculas de adhesión celular P-selectina and galectina-3 tienen un rol fundamental. El objetivo de esta trabajo fue estudiar las alteraciones en los mediadores de la remodelación ósea (RANKL, OPG, P-selectina and galectina-3) en un modelo de enfermedad renal crónica con tratamiento glucocorticoideo. Ratas Wistar hembras fueron divididos en 4 grupos: control (C); enfermedad renal crónica con afección de la remodelación ósea (ERC); animales con afección de la remodelación ósea expuestos a glucocorticoides (GC); enfermedad renal crónica con afección de la remodelación ósea tratados con glucocorticoides (ERC+GC). Los efectos de la ERC y los GC fueron evaluados bioquímicamente, histológicamente y por medición de la densidad ósea. RANKL, OPG, Pselectina and galectina-3 se cuantificaron en muestras de sangre venosa empleando enzimoinmuno análisis. En los 3 grupos experimentales la densidad ósea se evidenció reducida y los niveles séricos de RANKL elevados respecto al grupo control. Los niveles de OPG en los grupos ERC y GC fueron superiores mientras que en el grupo ERC+GC menores respecto a los animales controles. Galectina 3 plasmática en GC y ERC+GC se encontró reducida y aumentada en los animales ERC, en comparación con los animales controles. La concentración sérica de P-selectina sérica fue mayor en los grupos ERC y ERC+GC, y menor en los animales GC respecto a los niveles plasmáticos de los animales intactos. El avance del conocimiento sobre la regulación de la remodelación ósea a través de la interacción de mediadores sistémicos, en un futuro, puede conducir al desarrollo de nuevas estrategias terapéuticas para la prevención de la osteoporosis en pacientes con enfermedad renal crónica. (AU)

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)

Chronic kidney disease patients who smoke have higher serum phosphorus / Pacientes tabagistas com doença renal crônica apresentam fósforo sérico mais elevado

ABSTRACT Introduction: Mineral and bone metabolism disorders in chronic kidney disease (CKD-MBD) constitute a syndrome defined by changes in calcium, phosphorus (P), vitamin D and parathormone, fibroblast growth factor 23 (FGF-23) and its specific cofactor, Klotho. CKD-MBD, as well as smoking, are associated with an increased risk of cardiovascular disease. However, it is not known whether or not smoking impacts the cardiovascular risk in CKD- MBD. Objective: To analyze the relationship between smoking and CKD-MBD markers. Methods: We evaluated 92 patients divided into: 1) Control Group: non-smokers without CKD; 2) CKD group in stages III and IV under conservative treatment (20 non-smokers and 17 smokers); 3) CKD group on dialysis (21 non-smokers and 19 smokers). Clinical, demographic, and biochemical markers were compared between the groups. Results: FGF-23 and Klotho levels were not different between smokers and non-smokers. Patients in the CKD group on conservative treatment had higher serum P than non-smokers (p = 0.026) even after adjusted for renal function (p = 0.079), gender (p = 0.145) and age (p = 0.986). Conclusion: Smoking confers a higher cardiovascular risk to CKD patients under conservative treatment as it is associated with higher levels of P. Further studies are needed to confirm and better elucidate this finding.

RESUMO Introdução: Os distúrbios do metabolismo mineral e ósseo da doença renal crônica (DMO-DRC) constituem uma síndrome definida por alterações do cálcio, do fósforo (P), da vitamina D e do paratormônio, do fator de crescimento de fibroblastos 23 (FGF-23) e de seu cofator específico, Klotho. Os DMO-DRC, assim como o tabagismo, estão associados a maior risco de doença cardiovascular. Porém, não se sabe se há influência do tabagismo no risco cardiovascular dos DMO-DRC. Objetivo: Analisar a relação entre o tabagismo e marcadores dos DMO-DRC. Métodos: Avaliamos 92 pacientes divididos em: 1) Grupo controle sem DRC não tabagistas; 2) Grupo DRC em tratamento conservador estágios III e IV (20 não tabagistas e 17 tabagistas); 3) Grupo DRC em diálise (21 não tabagistas e 19 tabagistas). Marcadores clínicos, demográficos e bioquímicos foram comparados entre os grupos. Resultados: Níveis de FGF-23 e Klotho não foram diferentes entre tabagistas e não tabagistas. Pacientes tabagistas do grupo com DRC em tratamento conservador exibiram maior P sérico do que não tabagistas (p = 0,026) mesmo após ajuste para função renal (p = 0,079), sexo (p = 0,145) e idade (p = 0,986). Conclusão: O tabagismo confere um maior risco cardiovascular adicional aos pacientes com DRC em tratamento conservador à medida que se associa com maiores níveis de P. Novos estudos são necessários para confirmar e melhor elucidar esse achado.

Association of bone mineral density with chronic obstructive pulmonary disease in postmenopausal women

Abstract Background Osteoporosis (OP) is common in patients with chronic obstructive pulmonary disease (COPD). The relationship between OP and COPD has been primarily studied in male patients, and few reports are available in postmenopausal women. Objective The purpose of this study was to investigate the association between bone mineral density (BMD) and COPD in postmenopausal women. Methods This cross-sectional study included 133 clinically stable female ex-smokers with confirmed COPD, and 31 age-matched “ex-smoker” female controls. We analyzed groups according to their airway obstruction category. BMD was measured on dual-energy X-ray absorptiometry images of the left femoral neck. Results Patients with COPD had lower T-scores and higher prevalence of osteopenia/OP than the control group. In the COPD group, the airway obstruction category was significantly associated with the T-score after adjustment for confounders. Multivariate logistic regression analysis showed COPD was an independent marker for increased risk of osteopenia/OP in postmenopausal women. Conclusions COPD and airway obstruction category were strongly related to BMD. Postmenopausal women with COPD, especially those with severe airway obstruction, had a higher prevalence rate and a higher risk of osteopenia and OP than female controls without COPD.

Efecto del ranelato de estroncio sobre la densidad mineral ósea en hombres con osteoporosis / Effect of strontium ranelate on bone mineral density in men with osteoporosis

La osteoporosis afecta al 6-7% de la población masculina. Es alta la proporción de pacientes con fracturas sin diagnóstico previo de esta enfermedad. La mortalidad luego de una fractura es mayor en hombres que en población femenina; a pesar de esto, la mayoría de los pacientes no reciben tratamiento. Los fármacos aprobados, en nuestro medio, para tratar la osteoporosis masculina son: bifosfonatos, teriparatida y ranelato de estroncio. El objetivo de este estudio fue evaluar el efecto del ranelato de estroncio sobre la densidad mineral ósea en hombres después de 1 año de tratamiento. Se incluyeron los registros de 20 hombres de 67,8±3,0 años, tratados con ranelato de estroncio (2 g/día) durante 1 año. Todos los pacientes presentaban un T-score inferior a -2,5 en cadera o columna vertebral o un T-score inferior a -2,0 y factores de riesgo de fractura. No hubo modificación de parámetros de laboratorio luego del tratamiento (calcemia, calciuria, fósforo sérico, parathormona, 25(OH)vitamina D, fosfatasa alcalina y desoxipiridinolina) en relación a los basales. Luego del tratamiento con ranelato de estroncio se observó incremento de la densidad mineral ósea en columna lumbar: 0,953±0,029 versus 0,997±0,030 g/cm2 (p=0,0068), cuello femoral: 0,734±0,013 versus 0,764±0,016 g/cm2 (p=0,0084) y cadera total: 0,821±0,02 versus 0,834±0,02 g/cm2 (p=0,0419). Conclusión: el tratamiento con ranelato de estroncio produjo un incremento significativo de la densidad mineral ósea en columna lumbar y fémur proximal en hombres con osteoporosis. (AU)

Osteoporosis affects 6-7% of the male population. The proportion of patients with fragility fractures but without diagnosis of the disease is high. Mortality after hip fracture is higher in men than in women; in spite of this, most patients are left without treatment for osteoporosis. Drugs approved, for the treatment of osteoporosis in our country are bisphosphonates, teriparatide, and strontium ranelate (SrR). The objective of this study was to evaluate the effect of SrR on axial BMD in men after one year of treatment. We obtained pertinent data from medical registries of 20 men aged 67,8±3,0 years, treated with oral SrR (2 g/day) for 12 months. All patients had a T-score below -2,5 at the hip or the lumbar spine, or a T-score below -2,0 and one or more risk factors for fracture. The levels of serum calcium, phosphate, alkaline phosphatase, 25-hydroxyvitamin D, or PTH, or urinary calcium and desoxipyridinoline remained unchanged following SrR administration. After treatment with SrR there were significant increases in BMD at the lumbar spine: 0,953±0,029 versus 0,997±0,030 g/cm2 (p=0,0068), femoral neck: 0,734±0,013 versus 0,764±0,016 g/cm2 (p=0.0084), and total hip: 0,821±0,02 versus 0,834±0,02 g/cm2 (p=0,0419). Conclusion: in osteoporotic men, treatment with SrR significantly increases BMD in the lumbar spine and the proximal femur. (AU)

Osteoartrite: prevalência e presença de fatores associados em idosos ativos / Osteoarthritis: prevalence and presence of risk factors in elderly active

Objetivo: investigar a prevalência de osteoartrite e a presença de fatores associados em frequentadores de um centro de convivência. Metodologia: trata-se de um estudo transversal aninhado a um estudo de coorte realizado com 391 adultos e idosos em um centro de convivência e atenção para idosos, de julho/2014 a julho/2015. Foram consideradas as variáveis: presença de osteoartrite, sexo, idade, cor/raça, estado nutricional, quedas, autopercepção de saúde, início da menopausa e auto relato de doenças. Resultados: dos 391 participantes, 32 (8,5%) possuíam osteoartrite, 377 (96,4%) eram do sexo feminino, 187 (47,9%) com idade entre 60 e 69 anos, 326 (84,1%) cor branca, 191 (56,5%) baixo peso/eutrófico, 63 (16,1%) relataram quedas no último ano, 282 (72,2%) saúde muito boa/boa, 223 (53,9%) hipertensão e 306 (78,3%) das mulheres atingiram a menopausa após os 55 anos. A razão de prevalência da osteoartrite mostrou-se associada a pior percepção de saúde (RP=2,01), relato de quedas (RP=2,37), osteoporose/osteopenia (RP=8,35) e artrite reumatoide (RP=7,84) Conclusão: a osteoartrite mostrou-se prevalente em um indivíduo a cada 12 estudados, possivelmente pela condição fisicamente ativa da amostra, sugerindo a influência desta na manifestação da doença.

Objective: to investigate the prevalence of osteoarthritis and the presence of risk factors in a community center. Methodology: crosssectional study in a community center for the elderly, July/2014 to July/2015. They were considered: presence of osteoarthritis, sex, age, color/race, nutritional status, falls, perceived health, early menopause and self-reported disease. A descriptive and inferential analysis. Results: of the 391 participants, 8.5% had osteoarthritis, 96.4% were female, 47.9% aged between 60 and 69 years, 84.1% white, 56.5% underweight/normal weight, 16.1% reported falls in the last year, 72.2% health very good/good, 53.9% hypertension and 78.3% of women reached menopause after 55 years. The presence of osteoarthritis was associated with worse health perception (RP=2.01), history of falls (RP= 2.37), osteoporosis/osteopenia (RP=8,35) and rheumatoid arthritis (RP= 7,84). Conclusion: osteoarthritis was found to be prevalent in one subject every 12, possibly by physically active condition of the sample, suggesting its influence on the manifestation of the disease.

Reversal of uremic tumoral calcinosis by optimization of clinical treatment of bone and mineral metabolism disorder / Reversão da calcinose tumoral urêmica pela otimização do tratamento clínico da desordem do metabolismo ósseo e mineral

Abstract Tumoral calcinosis is an uncommon type of extraosseous calcification characterized by large rubbery or cystic masses containing calcium-phosphate deposits. The condition prevails in the periarticular tissue with preservation of osteoarticular structures. Elevated calcium-phosphorus products and severe secondary hyperparathyroidism are present in most patients with uremic tumoral calcionosis (UTC). Case report of an obese secondary to chronic glomerulonephritis, undergoing continuous ambulatory peritoneal dialysis (CAPD) reported the appearance of painless tumors in the medial surface of fifth finger and left arm. Tumoral calcinosis was confirmed by left biceps biopsy. Poor adherence to CAPD. The patient was transferred to the "tidal" modality of peritoneal dialysis and after was treated by hemodialysis, despite the persistence of severe hyperparathyroidism progressive reduction of UTC until near to its complete disappearance. Nowadays, one year after patient received deceased-donor kidney transplantation, he presents with an improvement in secondary hyperparathyroidism. UTC should be included in the elucidation of periarticular calcification of every patient on dialysis. Relevant laboratory findings such as secondary hyperparathyroidism and elevated calcium- phosphorus products in the presence of periarticular calcification should draw attention to the diagnosis of UTC.

Resumo A calcinose tumoral é um tipo raro de calcificação extraóssea caracterizada por grandes massas císticas e elásticas contendo depósitos de fosfato de cálcio. A condição é mais prevalente no tecido periarticular e preserva estruturas osteoarticulares. A elevação do produtos cálcio-fósforo e o hiperparatireoidismo secundário grave estão presentes na maioria dos pacientes com calcinose tumoral urêmica (UTC). O relato de caso em questão refere-se a um homem de 22 anos, branco, obeso, com doença renal crônica secundária à glomerulonefrite crônica, em diálise peritoneal ambulatorial contínua (CAPD), que apresentou aparecimento de tumores indolores na face medial do quinto quirodáctilio e braço esquerdo. A calcinose tumoral foi confirmada por biópsia do bíceps esquerdo. O paciente apresentava baixa adesão à CAPD. Foi transferido para a modalidade de diálise peritoneal e depois iniciou tratamento por hemodiálise. Apesar da persistência do hiperparatireoidismo grave, houve redução progressiva da UTC, com resolução próxima do seu desaparecimento completo. Há 1 ano o paciente foi submetido a transplante renal, doador falecido, e apresentou melhora do hiperparatiroidismo secundário. A UTC deve ser incluída na elucidação de calcificação periarticular de pacientes em diálise. Os achados laboratoriais relevantes, tais como hiperparatiroidismo secundário e elevação dos produtos cálcio-fósforo na presença de calcificação periarticular, devem chamar a atenção para o diagnóstico da UTC.

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.

Factors associated with subendocardial ischemia risk in patients on hemodialysis / Fatores associados ao risco de isquemia subendocárdica em pacientes em hemodiálise

Abstract Introduction: Bone metabolism disorder (BMD) and vascular dysfunction contribute to excess cardiovascular mortality observed in hemodialysis patients. Vascular dysfunction, a new marker of atherosclerosis, can play a role in this risk. Even though associated with higher mortality in the general population, such vascular evaluation in patients on hemodialysis has not been extensively studied. Methods: In this cross-sectional study, hemodialysis patients were submitted to flow-mediated dilation, subendocardial viability ratio (SEVR) and ejection duration index assessment, in order to estimate the impact of BMD markers on vascular dysfunction. Results: A matched cohort of patients with (n = 16) and without (n = 11) severe secondary hyperparathyroidism (SHPT) was studied. Additionally, time spent under severe SHPT was also evaluated. Patients with severe SHPT had lower SEVR and higher ejection duration index, indicating higher cardiovascular risk. Lower SEVR was also associated to diastolic blood pressure (r = 0.435, p = 0.049), serum 25-Vitamin-D levels (r = 0.479, p = 0.028) and to more time spent under severe secondary hyperparathyroidism (SHPT), defined as time from PTH > 500pg/ml until parathyroidectomy surgery or end of the study (r = -0.642, p = 0.027). In stepwise multiple regression analysis between SEVR and independent variables, lower SEVR was independently associated to lower serum 25-Vitamin-D levels (p = 0.005), female sex (p = 0.012) and more time spent under severe SHPT (p = 0.001) in a model adjusted for age, serum cholesterol, and blood pressure (adjusted r² = 0.545, p = 0.001). Conclusion: Subendocardial perfusion was lower in patients with BMD, reflecting higher cardiovascular risk in this population. Whether early parathyroidectomy in the course of kidney disease could modify such results still deserves further investigation.

Resumo Introdução: Distúrbios do metabolismo ósseo (DMO) e alterações da função vascular contribuem para a elevada mortalidade de pacientes em hemodiálise. A disfunção vascular, um novo marcador de aterosclerose, pode contribuir para este risco. Apesar de associada a aumento de mortalidade na população geral, a avaliação de tal disfunção ainda não foi realizada de modo amplo em pacientes em hemodiálise. Métodos: Neste estudo transversal, pacientes em hemodiálise foram submetidos à avaliação da vasodilatação mediada por fluxo, razão de viabilidade subendocárdica (RVSE) e índice de duração de ejeção, como estimativas de avaliação dos marcadores de DMO sobre disfunção vascular. Resultados: Uma coorte pareada com (n = 16) e sem (n = 11) hiperparatireoidismo secundário (HPTS) grave foi estudada. Adicionalmente, o tempo transcorrido do diagnóstico de HPTS grave também foi avaliado. Pacientes com HPTS grave apresentaram menores valores de RVSE e maiores valores de índice de duração de ejeção, apontando maior risco cardiovascular. Baixa RVSE também foi associada à pressão arterial diastólica (r = 0,435, p = 0,049), níveis séricos de 25-Vitamina D (r = 0,479, p = 0,028) e maior tempo transcorrido desde diagnóstico de HPTS grave, definido como tempo em que o paciente permaneceu com valores de paratormônio superiores a 500 pg/ml até realização de cirurgia de paratireoidectomia ou término do estudo (r = -0,642, p = 0,027). Em regressão logística stepwise entre RVSE e variáveis independentes, menor RVSE foi independentemente associado a menores valores de 25-Vitamina D (p = 0,005), sexo feminino (p = 0,012) e maior tempo transcorrido desde diagnóstico de HPTS grave (p = 0,001) em um modelo ajustado para idade, colesterol sérico e pressão arterial (r2 ajustado = 0,545, p = 0,001). Conclusão: A perfusão subendocárdica foi menor em pacientes com DMO, refletindo o maior risco cardiovascular nesta população. Investigações adicionais são necessárias para definir se a paratireoidectomia precoce no curso da doença renal crônica poderia interferir neste risco.

Osteoarticular diseases and physical performance of Brazilians over 80 years old / Doenças osteoarticulares e desempenho físicode idosos brasileiros com idade igual ou superior a 80 anos

Abstract Objective To investigate the physical performance of Brazilian individuals older than 80 years with and without OD. Methods The sample consisted of 135 individuals (aged > 80 years) of both gender. Identification of osteopenia/osteoporosis was verified by Dual Energy X-ray Absorptiometry, and the presence of others osteoarticular diseases (OD) was obtained using a questionnaire of morbidities. Physical performance was analyzed by motor tests. Results Men presented higher proportion of osteopenia/osteoporosis compared to women (p = 0.013). The proportion of older people with arthritis/osteoarthritis for women and men was 33% and 26%, respectively, and with OD in the spine was 19% and 12%, respectively. No significant difference for physical performance, measured by each test and overall score, was observed between groups of OD. According to gender, male with OD presented lower performance in gait speed, balance and overall score (p < 0.05), while older people with osteopenia/osteoporosis are at higher risk for low physical performance (OR 2.73; CI 95% 1.31-5.66). Conclusion In conclusion it was verified in older people with age of 80 years or more, a high prevalence of OD, especially in men, and the presence of these diseases interfered negatively their physical performance.

Resumo Objetivo Investigar o desempenho físico de idosos brasileiros com idade superior a 80 anos com e sem doenças osteoarticulares (DO). Métodos Foram avaliados 135 indivíduos (idade > 80 anos) de ambos os sexos. A presença de osteoporose foi analisada por meio da técnica de Absorptiometria de Raios-X de Dupla Energia, e a prevalência de outras doenças osteoarticulares foi verificada por meio de um questionário resumido de morbidades referidas. O desempenho físico foi avaliado por testes motores. Resultados Os homens apresentaram maior proporção de osteopenia/osteoporose comparados às mulheres (p = 0,013). A proporção de idosos com artrite/artrose foi 33% e 26%, e com alguma doença na coluna foi 19% e 12%, para homens e mulheres, respectivamente. Não houve diferença significativa no desempenho físico para a amostra geral. Segundo o sexo, homens com DO apresentaram menor desempenho nos testes de caminhada, equilíbrio e escore total (p < 0,05). Idosos com osteopenia/osteoporose apresentaram maior risco para limitação física (OR 2,73; IC 95% 1,31-5,66). Conclusão Foi verificado em idosos com idade igual ou superior a 80 anos alta prevalência de doenças osteoarticulares, especialmente em homens, e sua presença interfere negativamente no desempenho físico.

Psoriasis: new comorbidities

Abstract Psoriasis is a chronic inflammatory disease associated with several comorbidities. A few decades ago, it was considered an exclusive skin disease but today it is considered a multisystem disease. It is believed that 73% of psoriasis patients have at least one comorbidity. Studies have demonstrated the association of psoriasis with inflammatory bowel disease, uveitis, psychiatric disorders, metabolic syndrome and its components and cardiovascular diseases. The systemic inflammatory state seems to be the common denominator for all these comorbidities. This work aims at presenting a review of the current literature on some new comorbidities that are associated with psoriasis as osteoporosis, obstructive sleep apnea and chronic obstructive pulmonary disease. While there is still controversy, many studies already point to a possible bone involvement in patients with psoriasis, especially in the male group, generally less affected by osteoporosis. Psoriasis and chronic obstructive pulmonary disease present some risk factors in common as obesity, smoking and physical inactivity. Besides, both diseases are associated with the metabolic syndrome. These factors could be potential confounders in the association of the two diseases. Further prospective studies with control of those potential confounders should be developed in an attempt to establish causality. Existing data in the literature suggest that there is an association between obstructive sleep apnea and psoriasis, but studies performed until now have involved few patients and had a short follow-up period. It is, therefore, premature to assert that there is indeed a correlation between these two diseases.