Tumor pardo del paladar, presentación atípica de hiperparatiroidismo primario en adolescente: buena evolución y normalización de la masa ósea tras paratiroidectomía / Brown tumor of the palate, atypical presentation of primary hyperparathyroidism in an adolescent: good evolution and bone mass normalization after parathyroidectomy

El hiperparatiroidismo primario (HPTP) es poco frecuente en niños y adolescentes. Hay escasos datos para el manejo de estos pacientes en pediatría. Las glándulas paratiroideas son glándulas endocrinas que secretan hormona paratiroidea (PTH) y regulan el metabolismo del calcio y del fósforo. La sobreexpresión de PTH se llama hiperparatiroidismo, que se clasifica en primario, secundario y terciario. En los adolescentes, 80 a 92% de los hiperparatiroidismos primarios se deben a adenoma paratiroideo. Presentamos el caso clínico de una adolescente con una primera manifestación atípica de HPTP, la presencia de un tumor pardo del paladar, presentación rara de adenoma paratiroideo, acompañado de hipercalcemia, marcada elevación de PTH y varias lesiones óseas. (AU)

Primary hyperparathyroidism (PHPT) in children and adolescents is uncommon. Guidelines for management in pediatric patients are limited. Parathyroid glands are endocrine glands that secrete parathyroid hormone (PTH) and regulate calciumphosphate metabolism. The overexpression of PTH is called hyperparathyroidism, and is classified as primary, secondary, and tertiary. In adolescents, 80 to 92% of PHPT cases are due to a parathyroid adenoma. We present here a case report of an adolescent with a brown tumor of the palate as the first manifestation of the disease, atypical and rare presentation of parathyroid adenoma in an adolescent. She had hypercalcemia, marked elevation of PTH and bone lesions. (AU)

Marcadores óseos en niños y adolescentes / Bone markers in children and adolescents / Marcadores ósseos em crianças e adolescentes

Los marcadores óseos son moléculas específicas que pueden clasificarse en dos categorías: formación y resorción óseas. Cuando se los compara con los adultos, los niños tienen muy elevadas concentraciones de los marcadores óseos debido a la elevada velocidad de crecimiento y a la rápida remodelación ósea. No solo reflejan el crecimiento (modelación esquelética y crecimiento linear), sino también la remodelación ósea. Ningún marcador es específico para cada uno de estos procesos y no son fáciles de interpretar en niños y adolescentes dado que están influenciados por varios factores fisiológicos como edad, sexo, velocidad de crecimiento y estadio puberal. Es necesario conocer la velocidad de crecimiento y el desarrollo puberal para interpretar correctamente los resultados. Además, muestran variaciones diurnas en sus concentraciones con picos por la mañana y nadir por la tarde. A la actualidad, existe una variada referencia de datos de marcadores óseos en niños y adolescentes. Se presenta una revisión de hallazgos científicos de varios marcadores séricos y urinarios que reflejan la formación y resorción óseas durante la niñez y adolescencia. Los marcadores óseos son de mucha utilidad en investigación clínica y fisiología del metabolismo óseo, sin embargo, su uso de rutina en clínica aún no está bien establecido.

Bone markers are specific bone-derived molecules that can be classified into two categories: bone formation and bone resorption markers. Compared to adults, children have dramatically elevated bone marker concentrations due to high skeletal growth velocity and rapid bone turnover. They reflect growth (skeletal modelling) and remodelling and no marker is specific for any of the different biological processes of remodelling, modelling or epiphyseal growth. Bone turnover markers may not be easy to interpret in children as they are influenced by many physiological factors, such as age, gender, growth velocity, and pubertal stage. Knowledge of growth velocity and pubertal development is necessary to interpret the values of biological markers of bone turnover correctly. Turnover markers also show a diurnal variation, with a peak of concentrations in the morning and nadir of concentrations in the late afternoon. To date, a variety of pediatric references for bone markers have been reported. This review describes research findings on various sera and urine markers that reflect bone formation and resorption in children and adolescents. While bone markers are useful in research in the field of bone metabolism, their utility in routine clinical applications in pediatrics has not been established.

Marcadores ósseos são moléculas específicas que podem ser classificadas em duas categorias: formação e reabsorção óssea. Em comparação com os adultos, as crianças têm concentrações altamente elevadas de marcadores ósseos devido à alta velocidade de crescimento e à remodelação óssea rápida. Não só refletem o crescimento (modelagem esquelética e crescimento linear), mas também a remodelação óssea. Nenhum marcador é específico para cada um desses processos e não são fáceis de interpretar em crianças e adolescentes visto que estão influenciados por vários fatores fisiológicos, tais como idade, sexo, velocidade de crescimento e desenvolvimento púbere. É necessário o conhecimento da velocidade de crescimento e o desenvolvimento do púbere para interpretar corretamente os resultados. Além disso, mostram variações diurnas em suas concentrações com picos de manhã e nadir pela tarde. Atualmente, existe uma variada referência de dados de marcadores ósseos em crianças e adolescentes. Apresenta-se uma revisão de achados científicos de vários marcadores séricos e urinários que refletem a formação e reabsorção ósseas em crianças e adolescentes. Embora os marcadores ósseos sejam úteis na investigação clínica e fisiologia do metabolismo ósseo, sua utilidade em aplicações clínicas de rotina ainda não foi bem estabelecida.

Juvenile Paget's disease with heterozygous duplication within TNFRSF11A encoding RANK.

Mendelian disorders of RANKL/OPG/RANK signaling feature the extremes of aberrant osteoclastogenesis and cause either osteopetrosis or rapid turnover skeletal disease. The patients with autosomal dominant accelerated bone remodeling have familial expansile osteolysis, early-onset Paget's disease of bone, expansile skeletal hyperphosphatasia, or panostotic expansile bone disease due to heterozygous 18-, 27-, 15-, and 12-bp insertional duplications, respectively, within exon 1 of TNFRSF11A that encodes the signal peptide of RANK. Juvenile Paget's disease (JPD), an autosomal recessive disorder, manifests extremely fast skeletal remodeling, and is usually caused by loss-of-function mutations within TNFRSF11B that encodes OPG. These disorders are ultra-rare. A 13-year-old Bolivian girl was referred at age 3years. One femur was congenitally short and curved. Then, both bowed. Deafness at age 2years involved missing ossicles and eroded cochleas. Teeth often had absorbed roots, broke, and were lost. Radiographs had revealed acquired tubular bone widening, cortical thickening, and coarse trabeculation. Biochemical markers indicated rapid skeletal turnover. Histopathology showed accelerated remodeling with abundant osteoclasts. JPD was diagnosed. Immobilization from a femur fracture caused severe hypercalcemia that responded rapidly to pamidronate treatment followed by bone turnover marker and radiographic improvement. No TNFRSF11B mutation was found. Instead, a unique heterozygous 15-bp insertional tandem duplication (87dup15) within exon 1 of TNFRSF11A predicted the same pentapeptide extension of RANK that causes expansile skeletal hyperphosphatasia (84dup15). Single nucleotide polymorphisms in TNFRSF11A and TNFRSF11B possibly impacted her phenotype. Our findings: i) reveal that JPD can be associated with an activating mutation within TNFRSF11A, ii) expand the range and overlap of phenotypes among the Mendelian disorders of RANK activation, and iii) call for mutation analysis to improve diagnosis, prognostication, recurrence risk assessment, and perhaps treatment selection among the monogenic disorders of RANKL/OPG/RANK activation.

Ocular manifestations of juvenile Paget disease.

OBJECTIVES: To determine the prevalence and spectrum of retinal changes in juvenile Paget disease. METHODS: Observational case series and literature review with analysis. Patients with clinical and molecular evidence of juvenile Paget disease were recruited by members of the International Hyperphosphatasia Collaborative Group. Participants underwent ophthalmic examinations consisting of at least best-corrected Snellen visual acuity and dilated fundal examination or color fundus photography. A MEDLINE literature search was performed, and all identified case reports were reviewed for information regarding ocular phenotype. RESULTS: Fourteen eyes from 7 patients were examined. The mean (SD) patient age was 22 (8) years, and 4 patients were female. Retinal abnormalities were evident in 12 of 14 eyes and were reported among an additional 12 patients in the literature. Retinal abnormalities included mottling of the retinal pigment epithelium, peripapillary atrophy, angioid streaks, and choroidal neovascularization. Cumulative number of retinal abnormalities was strongly associated with increasing age. CONCLUSIONS: Juvenile Paget disease is associated with progressive retinopathy characterized by the development of angioid streaks, which may be complicated by choroidal neovascularization, the predominant cause of visual loss. Osteoprotegerin or its signaling pathway may have a role in calcification of Bruch membrane and in the pathogenesis of angioid streaks. Retinopathy in patients with juvenile Paget disease may be a sign of a more generalized vascular disorder.

Osteogénesis imperfecta: tratamiento con bisfosfonatos / Imperfect osteogenesis: treatment with bisphosphonates

El tratamiento con bifosfonatos (BP), ha mejorado la calidad de vida de los pacientes con osteogénesis imperfecta (OI). Los efectos benéficos son el alivio del dolor, la reducción de la incidencia de fracturas, la mejor movilidad corporal y la recuperación en las formas vertebrales. El tratamiento es más efectivo durante el período de crecimiento. Sin embargo hay preguntas que aún no tienen respuesta en relación al tiempo que deberá instituirse el tratamiento, si la vía oral es tan efectiva como la endovenosa, cuál es la mejor dosis, cuándo se deberá suspender el tratamiento, si se conservará la integridad del tejido óseo después de un tratamiento prolongado y cuáles fenómenos ocurren en el tejido óseo después de la interrupción de la terapia.

Profilaxis de raquitismo en niños sanos de Ushuaia. Efecto de dos dosis de 100.000 UI de vitamina D durante el invierno / Rickets prophylaxis in healthy children fron Usuahia. Effect of 2 doses of 100.000 UI of vitamin D during winter

Como provilaxis de raquitismo, se administró a niños sanos de Ushuaia (55ºS), una doble suplemenación de vitamina D de 100.000 UI al inicio del invierno (marzo 2004), y tres meses después durante el invierno (junio 2004). Se midió 25-hidroxivitamina D sérica (250HD) antes, 1 mes después de la primera suplementación, y 3 meses después de la segunda suplementación (marzo, abril y septiembre). Se estudiaron 18 niños sanos, edad (media más menos DS) 7.3 más menos 4.4 años (rango 1.2 a 14.6), 7 niñas y 11 niños. Antes del tratamiento, la 250 HD sérica fue 29.3 más menos 5.9 ng/ml. Aumentó significativamente 1 mes después de la primera suplementación (Abril): 35.3 más menos 4.4 ng/ml (p<0.001), y disminuyo significativamente 3 meses después de la segunda suplementación 22.4 más menos 4.6 ng/ml (Septiembre (p<0.01). Ningún niño tuvo deficiencia (<10 ng/ml) ni insuficiencia (10-15 bg/ml) de vitamina D. En abril, 1 mes después de la primera suplementación, ningún niño tuvo intoxicación de vitamina D (>50 ng/ml). Conclusión: los resultados sugieren que la doble suplementación con 100.000 UI de vitamina D durante otoño e invierno, previene la deficiencia de vitamina D de niños que habitan en zonas de riesgo del sur de nuestro país.

[Treatment of osteogenesis imperfecta with bisphosphonates]. / Tratamiento de osteogénesis imperfecta con bisfosfonatos.

Treatment with bisphosphonates (BP) improves the quality of life of patients with osteogenesis imperfecta (OI). Beneficial effects are the relief of bone pain, a reduction of fracture incidence, improvement of corporal mobility and recovery of normal vertebral form. Treatment is less effective after completion of growth [corrected] An update of the literature is here presented. A number of important unsolved questions have been pointed out: for how long should treatment be instituted? Is the oral route as effective as the intravenous one? Which is the best dose? When treatment should be stopped? How well preserved is the longterm integrity of the bones? Which are the phenomena occurring in bone tissue after interruption of therapy?

Tratamiento de osteogénesis imperfecta con bisfosfonatos / Treatment of osteogenesis imperfecta with bisphosphonates

El tratamiento con bisfosfonatos (BP), ha mejorado la calidad de vida de los pacientes con osteogénesis imperfecta (OI). Los efectos benéficos son el alivio del dolor, la reducción de la incidencia de fracturas, la mejor movilidad corporal y la recuperación en las formas vertebrales. El tratamiento es más efectivo durante el período de crecimiento. Se presenta una actualización del tema. De la lectura de los anales se destacan los siguientes interrogantes: ¿Por cuánto tiempo deberá instituirse el tratamiento? ¿Es la vía oral tan efectiva como la endovenosa? ¿Cuál es la mejor dosis? ¿Cuándo suspender el tratamiento? ¿Se conservará la integridad del tejido óseo después de un tratamiento prolongado? ¿Qué fenómenos ocurren en el tejido óseo después de la interrupción de la terapia?.(AU)

Treatment with bisphosphonates (BP) improves the quality of life of patients with osteogenesis imperfecta (OI). Beneficial effects are the relief of bone pain, a reduction of fracture incidence, improvement of corporal mobility and recovery of normal vertebral form. Treatment is less effective after completion of growth is here. An update of the literature is here presented. A number of important unsolved questions have been pointed out: for how long should treatment be instituted? Is the oral route as effective as the intravenous one? Which is the best dose? When treatment should be stopped? How well preserved is the longterm integrity of the bones? Which are the phenomena occurring in bone tissue after interruption of therapy?.(AU)

Tratamiento de osteogénesis imperfecta con bisfosfonatos / Treatment of osteogenesis imperfecta with bisphosphonates

El tratamiento con bisfosfonatos (BP), ha mejorado la calidad de vida de los pacientes con osteogénesis imperfecta (OI). Los efectos benéficos son el alivio del dolor, la reducción de la incidencia de fracturas, la mejor movilidad corporal y la recuperación en las formas vertebrales. El tratamiento es más efectivo durante el período de crecimiento. Se presenta una actualización del tema. De la lectura de los anales se destacan los siguientes interrogantes: ¿Por cuánto tiempo deberá instituirse el tratamiento? ¿Es la vía oral tan efectiva como la endovenosa? ¿Cuál es la mejor dosis? ¿Cuándo suspender el tratamiento? ¿Se conservará la integridad del tejido óseo después de un tratamiento prolongado? ¿Qué fenómenos ocurren en el tejido óseo después de la interrupción de la terapia?.

Treatment with bisphosphonates (BP) improves the quality of life of patients with osteogenesis imperfecta (OI). Beneficial effects are the relief of bone pain, a reduction of fracture incidence, improvement of corporal mobility and recovery of normal vertebral form. Treatment is less effective after completion of growth is here. An update of the literature is here presented. A number of important unsolved questions have been pointed out: for how long should treatment be instituted? Is the oral route as effective as the intravenous one? Which is the best dose? When treatment should be stopped? How well preserved is the longterm integrity of the bones? Which are the phenomena occurring in bone tissue after interruption of therapy?.

[Severe osteoporosis with vertebral crushes in juvenile dermatomyositis. Effect of oral alendronate therapy]. / Osteoporosis grave con aplastamientos vertebrales en dermatomiositis juvenil. Efecto del tratamiento con alendronato oral.

Glucocorticoids are used for the treatment of inflammatory and autoimmune diseases, cancer, and in prevention of organ rejects. A frequent secondary effect of longterm treatment with corticoids is the loss of bone mass, caused by several mechanisms: decrease in the intestinal calcium absorption, increase of the renal calcium excretion at the distal renal tubule, suppressive effect on the osteoblast and also in apoptosis of osteoclasts, inhibition in local production of IGF I (Insulin-like growth factor) and IGFBPs (binding IGF I proteins necessary for bone metabolism), and decrease on osteocalcin production. Longterm treatment with corticoids is associated with osteoporosis and vertebral fractures. To improve this condition, treatment with bisphosphonates has been proposed. We present here a clinical case of a girl with dermatomyositis and severe osteoporosis with vertebral crushes, who responded well to oral bisphophonate treatment.

Osteoporosis grave con aplastamientos vertebrales en dermatomiositis juvenil: efecto del tratamiento con alendronato oral / Severe osteoporosis with vertebral crushes in juvenile dermatomyositis: effect of oral alendronate therapy

Los glucocorticoides son usados comúnmente para el tratamiento de enfermedades inflamatorias, autoinmunes, enfermedades malignas, y en la prevención de rechazo de órganos trasplantados. Un efecto secundario frecuente del tratamiento prolongado es la pérdida de masa ósea que se produce por varios mecanismos y es causa de osteoporosis y fracturas vertebrales. El tratamiento con disfosfonatos ha sido propuesto para esta situación. Presentamos un caso clínico de osteoporosis grave en una niña con dermatomiositis juvenil, que respondió favorablemente al tratamiento con disfosfonatos orales.(AU)

Glucocorticoids are used for the treatment of inflammatory and autoimmune diseases, cancer, and in prevention of organ rejects. A frequent secondary effect of longterm treatment with corticoids is the loss of bone mass, caused by several mechanisms: decrease in the intestinal calcium absorption, increase of the renal calcium excretion at the distal renal tubule, suppressive effect on the osteoblast and also in apoptosis of osteoclasts, inhibition in local production of IGF I (Insulin-like growth factor) and IGFBPs (binding IGF I proteins necessary for bone metabolism), and decrease on osteocalcin production. Longterm treatment with corticoids is associated with osteoporosis and vertebral fractures. To improve this condition, treatment with bisphosphonates has been proposed. We present here a clinical case of a girl with dermatomyositis and severe osteoporosis with vertebral crushes, who responded well to oral bisphophonate treatment.(AU)

Osteoporosis grave con aplastamientos vertebrales en dermatomiositis juvenil: efecto del tratamiento con alendronato oral / Severe osteoporosis with vertebral crushes in juvenile dermatomyositis: effect of oral alendronate therapy

Los glucocorticoides son usados comúnmente para el tratamiento de enfermedades inflamatorias, autoinmunes, enfermedades malignas, y en la prevención de rechazo de órganos trasplantados. Un efecto secundario frecuente del tratamiento prolongado es la pérdida de masa ósea que se produce por varios mecanismos y es causa de osteoporosis y fracturas vertebrales. El tratamiento con disfosfonatos ha sido propuesto para esta situación. Presentamos un caso clínico de osteoporosis grave en una niña con dermatomiositis juvenil, que respondió favorablemente al tratamiento con disfosfonatos orales.

Glucocorticoids are used for the treatment of inflammatory and autoimmune diseases, cancer, and in prevention of organ rejects. A frequent secondary effect of longterm treatment with corticoids is the loss of bone mass, caused by several mechanisms: decrease in the intestinal calcium absorption, increase of the renal calcium excretion at the distal renal tubule, suppressive effect on the osteoblast and also in apoptosis of osteoclasts, inhibition in local production of IGF I (Insulin-like growth factor) and IGFBPs (binding IGF I proteins necessary for bone metabolism), and decrease on osteocalcin production. Longterm treatment with corticoids is associated with osteoporosis and vertebral fractures. To improve this condition, treatment with bisphosphonates has been proposed. We present here a clinical case of a girl with dermatomyositis and severe osteoporosis with vertebral crushes, who responded well to oral bisphophonate treatment.

Twice single doses of 100,000 IU of vitamin D in winter is adequate and safe for prevention of vitamin D deficiency in healthy children from Ushuaia, Tierra Del Fuego, Argentina.

In order to improve vitamin D status of children from Ushuaia (55 degrees S), at the South of Argentina, double supplementation with 100.000 IU of vitamin D was administered at the beginning of winter (March 2004), and 3 months later during winter (June 2004). In 2004, serum 25-hydroxyvitamin D (25OHD) was measured before the first supplementation, a month after, and 3 months after receiving the second supplementation (March, April and September). We studied 18 healthy children from Ushuaia, age (mean+/-S.D.) 7.3+/-4.4 years old (range 1.2-14.6), seven girls and 11 boys. Before treatment, serum 25OHD was 29.3+/-5.9 ng/ml. It increased significantly 1 month after the first supplementation (April): 35.3+/-4.4 ng/ml (p<0.001), and decreased significantly 3 months after the second supplementation: 22.4+/-4.6 ng/ml (September (p<0.001). No child was neither deficient (<10 ng/ml) nor insufficient (10-15 ng/ml) of vitamin D. On April, a month after the first supplementation, no children had vitamin D intoxication levels (>50 ng/ml). These results disclosed that to prevent vitamin D deficiency for children at zones of risk at the south of our country, double supplementation of 100,000 IU of vitamin D during autumn and winter, would be adequate and safe.

[Evolution of children one year post liver transplant]. / Evolución de niños post-trasplante hepático luego del primer año de sobrevida.

Orthotopic liver transplantation is the only definitive mode of therapy for children with end-stage liver disease. However, it remains challenging because of the necessity to prevent long-term complications. The aim of this study was to analyze the evolution of transplanted patients with more than one year of follow up. Between November 1992 and November 2001, 238 patients underwent 264 liver transplantations. A total of 143 patients with more than one year of follow up were included. The median age of patients +/- SD was 5.41 years +/- 5.26 (r: 0.58-21.7 years). All children received primary immunosuppression with cyclosporine. The indications for liver replacement were: fulminant hepatic failure (n: 50), biliary atresia (n: 38), cirrhosis (n: 37), chronic cholestasis (n: 13) and miscellaneous (n: 5). The indications for liver re-transplantation were: biliary cirrhosis (n: 7), hepatic artery thrombosis (n: 4) and chronic rejection (n: 3). Reduced-size liver allografts were used in 73/157 liver transplants, 14 of them were from living-related donors and 11 were split-livers. Patient and graft survival rates were 93% and 86% respectively. Death risk was statistically higher in retransplanted and reduced-size grafted patients. Growth retardation and low bone density were recovered before the first 3 years post-transplant. The incidence of lymphoproliferative disease was 7.69%. De novo hepatitis B was diagnosed in 7 patients (4.8%). Social risk did not affect the outcome of our population. The prevention, detection and early treatment of complications in the long-term follow up contributed to improve the outcome.

Evolución de niños post-trasplante hepático luego del primer año de sobrevida. / [Evolution of children one year post liver transplant]

Orthotopic liver transplantation is the only definitive mode of therapy for children with end-stage liver disease. However, it remains challenging because of the necessity to prevent long-term complications. The aim of this study was to analyze the evolution of transplanted patients with more than one year of follow up. Between November 1992 and November 2001, 238 patients underwent 264 liver transplantations. A total of 143 patients with more than one year of follow up were included. The median age of patients +/- SD was 5.41 years +/- 5.26 (r: 0.58-21.7 years). All children received primary immunosuppression with cyclosporine. The indications for liver replacement were: fulminant hepatic failure (n: 50), biliary atresia (n: 38), cirrhosis (n: 37), chronic cholestasis (n: 13) and miscellaneous (n: 5). The indications for liver re-transplantation were: biliary cirrhosis (n: 7), hepatic artery thrombosis (n: 4) and chronic rejection (n: 3). Reduced-size liver allografts were used in 73/157 liver transplants, 14 of them were from living-related donors and 11 were split-livers. Patient and graft survival rates were 93

and 86

respectively. Death risk was statistically higher in retransplanted and reduced-size grafted patients. Growth retardation and low bone density were recovered before the first 3 years post-transplant. The incidence of lymphoproliferative disease was 7.69

. De novo hepatitis B was diagnosed in 7 patients (4.8

). Social risk did not affect the outcome of our population. The prevention, detection and early treatment of complications in the long-term follow up contributed to improve the outcome.