Caso clínico: hipofosfatasia de la niñez. Seguimiento clínico / Clinical case: childhood hypophosphatasia. Clinical follow-up

La hipofosfatasia (HP) es una enfermedad congénita, causada por mutaciones con pérdida de función en el gen ALPL que codifica la isoenzima no específica de tejido de la fosfatasa alcalina (TNSALP). Su expresión clínica es muy variable, desde casos de muerte intraútero por alteración grave de la mineralización ósea, hasta casos solo con caída prematura de la dentición. Se presenta el caso clínico de un varón al que se le diagnosticó odontohipofosfatasia a los 30 meses por pérdida temprana de piezas dentarias y niveles anormalmente bajos de fosfatasa alcalina, sin signos de raquitismo ni deformidades óseas. Durante su seguimiento, hasta los 13 años, presentó síntomas compatibles con HP infantil leve, como cansancio al caminar, incoordinación en la marcha y dolor en miembros inferiores que aumentaban con la actividad física. Ante la aparición de edema bimaleolar y poca respuesta al tratamiento con calcitonina y antiinflamatorios, se descartaron patologías infecciosas o reumáticas o ambas y se diagnosticó, por biopsia de tibia y peroné, periostitis sin detección de cristales de pirofosfato. Los controles radiológicos durante su evolución mostraron ensanchamiento metafisario en muñeca, falta de remodelado de metacarpianos, hojaldrado perióstico en tibia y peroné e hipomineralización en metáfisis tibiales, con "lenguas radiolúcidas" características de HP. Como conclusión, la hipofosfatasia debe considerarse como una entidad clínica para descartar en niños que presentan pérdida temprana de dientes. La presencia de este cuadro clínico es en general suficiente para realizar el diagnóstico de HP de la niñez. (AU)

Hypophosphatasia (HP) is a congenital disease, caused by mutations with loss of function in the gene ALPL that encodes the non-specific tissue isoenzyme of alkaline phosphatase (TNSALP). Its clinical expression displays considerable variability, from cases of intrauterine death due to severe alteration of bone mineralization, to cases with only early loss of teeth. We report the case of a male, diagnosed as odontohypophosphatasia at 30 months of age due to early loss of teeth and abnormally low levels of alkaline phosphatase, without signs of rickets or bone deformities. During follow-up, up to 13 years of age, he presented symptoms consistent with mild infantile HP such as tiredness when walking, lack of gait coordination, and pain in lower limbs, especially after physical activity. Due to the appearance of bimalleolar edema and poor response to treatment with calcitonin and anti-inflammatory drugs, infectious and / or rheumatic pathologies were ruled out. Periostitis without pyrophosphate crystal detection was diagnosed by tibial and fibular biopsy. Radiological controls during follow up showed metaphyseal wrist enlargement, lack of remodeling of metacarpals, periosteal flaking in the tibia and fibula and hypomineralization in the tibial metaphysis, with "radiolucent tongues"; characteristic of HP. In conclusion, hypophosphatasia should be considered as a clinical entity in children who present early loss of teeth. The presentation of this clinical case is generally sufficient to make the diagnosis of childhood HP. (AU)

[Effects of calcitonin nasal spray on serum bone resorptive marker CTX and other laboratory findings in osteopenic menopausal women: a clinical trial]

Various therapeutic options such as calcitonin have been suggested for patients with low bone density, despite uncertain efficacy in most patients. C-telopeptide of type I collagen [CTX] is a new bone marker used for the assessment of bone resorption. The aim of this study was to evaluate the therapeutic effects of nasal spray calcitonin in women with osteopenia via serum CTX and other laboratory tests. We conducted a self controlled clinical trial in 2009 on 105 women of menopausal age diagnosed in Baqiyatallah Hospital Clinic with osteopenia based on a bone mineral density score of 1.5 SD lower than peak bone mass. The patients were assigned to receive nasal spray calcitonin [200 IU/day], calcium [1000 mg/day] and Vit-D [400 IU/day] for 6 months. Serum CTX and other laboratory parameters were measured before and after the treatment. The data were analyzed by SPSS, version 17, using t-tests and a P<0.05 was considered statistically significant. Fifty-two patients completed the study and the mean CTX level decreased significantly from 3.10 +/- 2.03 to 2.61 +/- 1.82 pmol/lit [P<0.001], but total serum levels of PTH, Ca, AST, ALT and Alkaline Ph decreased insignificantly. It seems that nasal spray of calcitonin is significantly effective in preventing disease progression and treatment of low bone density by inhibiting bone tissue resorption indicated by CTX although further studies with larger samples sizes and inclusion of control groups are warranted

Short term results of concomitant intranasal administration of salmon calcitonin in intertrochanteric femur fractures operated upon using dynamic hip screw

To evaluate the effect of nasal calcitonin spray in union of the intertrochanteric fractures of elderly female patients. Fifty female patients aged above 60 years [mean age = 73.9 years] old with Intertrochanteric fracture were operated from Sept 2005 to August 2006 by dynamic hip screw. In a randomized controlled trial, patients were divided into two groups A and B. Each group had 25 patients. After hospitalization 200 IU of salmon calcitonin as a single dose nasal spray was administered to patients of group A, daily for 3 months and a placebo spray was used in patients of group B. serum level of alkaline phosphatase and time of appearance of a bone callus in a plain radiograph were compared in the two groups twice weekly for 8 weeks. About 72% of patients in group A showed signs of union as the appearing of bone callus in radiograph in the 3rd week, compared to 40% in group B. Twenty of patients in group A [80%] and 20% of the group B had an increase in serum alkaline phosphatase from the 15th day after injury [P<0.005]. Meanwhile alkaline phosphatase levels in group A was 185 IU on 15 the day compared to 140 IU on group B. and values were 443 IU and 210 IU on 90th day respectively. As regards the time of appearance of the union signs in a plain bone radiograph, 72% of patients in group A have shown signs of appearance of a bone callus in the 3rd week after surgery, while the rate has been 40% in group B. Using nasal spray of calcitonin in old females with intertrochanteric fracture is effective for earlier and increased rate of bone union

The Efficacy of Physical Therapy and Physical Therapy Plus Calcitonin in the Treatment of Lumbar Spinal Stenosis

PURPOSE: The aim of our study was to compare the efficacy of physical therapy alone and in combination with calcitonin in patients with neurogenic claudication (NC). MATERIALS AND METHODS: In this single blind, and randomized study, patients with lumbar spinal canal stenosis who were diagnosed by clinical findings and MRI and having NC were included. Patients were observed for 8 weeks and evaluated before and after treatment. Patients were randomized between the salmon calcitonin 200 U/day + physical therapy (n = 23) (Group 1) and paracetamol 1,500 mg/day + physical therapy (n = 22) (Group 2) treatment groups. Both groups received the same physical therapy (interferential current + hot pack + short wave diathermy) and exercise protocol. The association of various clinical and functional parameters was assessed statistically by using paired and unpaired t test, chi square test and McNemar's test. p 0.05). After 8 weeks of treatment, both groups benefited significantly with respect to VAS, functional status and walking distance (p 0.05). CONCLUSION: In 45 patients with lumbar spinal stenosis who received 8 weeks of treatment, concomitant use of calcitonin with physical therapy and exercise did not have any benefical effect on the patient's pain, functional status, lumbar mobility and walking distance.

Aneurysmal bone cyst at C2: imaging evaluation after intralesional injection of calcitonin and methylprednisolone / Cisto ósseo aneurismático em C2: avaliação por imagem após injeção intralesional de calcitonina e metilprednisolona

Objective: To demonstrate imaging findings during the follow-up of patients with aneurysmal bone cyst (ABC) of C2 treated with intralesional injection of calcitonin and methylprednisolone. METHOD: Three patients with ABC of C2 were treated percutaneously with intralesional injection of calcitonin and methylprednisolone. All the patients were females, with ages varying from 6 to 13 years. All of them presented with cervical masses, but without neurological symptoms. RESULTS: Imaging follow-up with CT and plain films showed progressive ossification and reduction of the blood-filled cavities with volume reduction of all lesions. No recurrence was noted during the follow-up.  Conclusion: Intralesional injection of calcitonin and methylprednisolone is a safe treatment option for cervical ABC. The CT scan is especially valuable as a guide of injection site and for the follow-up of ossification of the treated ABCs.

OBJETIVO: Demonstrar os aspectos de imagem no acompanhamento de pacientes submetidos ao tratamento de cisto ósseo aneurismático com injeção intralesional de calcitonina e metilprednisolona. MÉTODO: Três pacientes com cisto ósseo aneurismático em C2 foram tratados com injeção intralesional percutânea de calcitonina e metilprednisolona. Os três pacientes eram do sexo feminino com idades variando de 6 a 13 anos. Os três pacientes apresentavam massa cervical sem sintomas neurológicos. RESULTADOS: O acompanhamento por imagem com tomografia computadorizada e radiografia simples demonstrou ossificação progressiva e redução das cavidades preenchidas por sangue, com redução do volume das lesões. Não foi percebida recidiva durante o acompanhamento. CONCLUSÃO: A injeção intralesional de calcitonina e metilprednisolona é uma opção de tratamento segura para o cisto ósseo aneurismático cervical. A tomografia computadorizada é especialmente útil para orientar o sítio da punção e para o acompanhamento da ossificação dos cistos ósseos aneurismáticos tratados.

Calcitonina inibe os efeitos benéficos da estimulação elétrica no músculo esquelético / Calcitonin inhibit the beneficial effects of electric stimulation in skeletal muscle

Durante o tratamento de doenças ósseas com calcitonina sintética, observa-se um efeito diabetogênico, particularmente nos tratamentos com calcitonina de salmão (CS). Neste estudo foi analisado o efeito da administração de CS(1U/kg) sobre o teste de tolerância à glicose (GTT), concentração plasmática de insulina (I), ácidos graxos livres (AGL), glicemia (GLI) e reservas musculares de glicogênio (RG). Foi avaliado, ainda, o efeito da estimulação elétrica (EE; 10Hz, i=0,3ms, 20min/dia) em músculos tratados ou não com CS. Foram utilizados 24 ratos machos tratados durante 10 dias com CS e/ou EE. A determinação da I foi realizada através de radioimunoensaio, enquanto as RG pelo método do fenol sulfúrico e as concentrações plasmáticas GLI e de AGL através de testes de laboratório. As ilhotas de Langerhans foram isoladas pelo método da colagenase e perfundidas para coleta do efluxo do 87Rb. Neste estudo, o grupo tratado com CS apresentou elevação na GLI e redução na I. As áreas da curva do GTT foram de 9.327 foram de 9.327mg/60min no grupo controle vs 17.665 mg/60 min no grupo tratado com CS. Tanto I quanto o AGL foram significativamente reduzidas por CS, enquanto as RG foram aumentadas pela EE e reduzidas pela CS. No grupo com associação do tratamento CS+EE, houve redução na síntese da RG e inibição da secreção de I, estimulada pela GLI. Assim, sugerimos que pacientes submetidos a tratamento com CS merecem uma atenção diferenciada quando submetidos a tratamento fisioterapêtico

A Comparison of Estrogen and Two Different Doses of Calcitonin in Ovariectomized Rats

The purpose of this study was to investigate the treatment efficacies of salmon calcitonin (SC) and estrogen in a type-I osteoporotic rat model. Sixty, 3-month-old, female Wistar rats were divided into six groups. The first group was used as the control, and the second a sham, the other four were surgically ovariectomized. 24 hours after the ovariectomy, they were either left untreated (OVX), or treated with an injection of either 17-beta estradiol (E2) 30 mcg/kg/24 hours, low-dose calcitonin (LDC) 10 IU/ kg/48 hours or high-dose calcitonin (HDC) 20 IU/kg/48 hours. 6 weeks later, the bone densities were measured by DEXA, the animals sacrificed and the femurs harvested for histomorphometric evaluation. The bone mineral densities (BMD) of the spine and proximal femur were lower in the OVX group, but only the values of the spine BMD were statistically significant. The BMD of the spine seemed to be preserved with all the treatments. The histomorphometric evaluation revealed that after the OVX the decrease in the trabecular volume was prevented by all the treatments. However, significant changes in the indices of bone formation were not shown. In conclusion, all the treatments prevented bone lost in the ovariectomized rats. Histopathological measurements of bone formation are unlikely to provide any evidence for the effects of these agents on the osteoblastic function. In the animal model of estrogen depletion, our results suggest that the calcitonin provides an important alternative therapy for postmenopausal osteoporosis.

study on the effect of calcitonin administration on hypophyseal - testicular axis in rats

The present study was designated to clarify the effect of calcitonin [CT] on the hypophysial testicular axis. A total number of forty adult male albino rats were used and they were classified into three main groups. The first group [control group] consisted of 10 adult male albino rats, which were injected intramuscularly with saline allover the period of experiment. The second group: [sCT-, administered group] consisted of 10 adult male albino rats, which were injected with sCT intramuscularly on alternative days, in a dose of 10 U/kg body weight/days for 4 weeks at 10 AM. However the third group [orchidectomized group consisted of 20 adult male rats. This third group was subdivided into two equal groups: Orchidectomized control group which was injected intramuscularly with saline, two weeks after the operation, for four weeks and Orchidectomized CT-administered group which were injected intramuscularly with sCT, two weeks after the operation, on alternative days in a dose of 10 U/kg body weight day for 4 week at 10 AM. The plasma levels of FSH, LH and testosterone were estimated [by radioimmunoassay] and the Ca[2+] plasma levels were estimated [by Clorometric method] for all groups. Also, histopathological examination was performed for the testes of the first and second groups to evaluate the local effect of CT and also to identify the effect of change in plasma gonadotropin levels on the testes.The results of these investigations showed that, the testosterone plasma levels were significantly decreased in healthy group after sCT administration, the FSH and LH plasma levels were significantly decreased in both healthy and orchidectomized groups after sCT administration and sCT administration caused insignificant change in Ca[2+] plasma levels in both healthy and orchidectomized groups after sCT administration. The histopathological study revealed that sCT administration caused thickening of the basement membrane of the seminiferous tubules in 20% of the total number of rats treated with sCT, thickening of the basement membrane and replacement of the interstitial cells of Leydig by halonosis in 50% of the total number of rats treated with sCT and thickening of the basement membrane, replacement of the interstitial cells of Leydig by halonosis and spermatic arrest at the stage of secondary spermatocytes in 30% of the total number of rats treated with sCT. From the above results, it could be concluded that CT administration resulted in a significant reduction in testosterone plasma levels that may be through a reduction in pituitary gonadotropins secretion and through a direct effect on the testes

Osteoporosis vertebral inducida por corticoides y ciclosporina en una paciente con enfermedad de Still / Vertebral osteoporosis induced by corticoids and cyclosporine in a patient with Still diseases

Se presenta el caso de una paciente de 29 años quien recibió prednisona y ciclosporina en altas dosis como tratamiento de la enfermedad de Still. Consultó por dolores invalidantes. Se comprobaron fracturas vertebrales múltiples, densidad mineral ósea lumbar descendida en rango de osteoporosis, alta remodelación ósea e hipercalciuria. Fue tratada con pamidronato por vía endovenosa (225 mg en tres meses), calcitonina nasal (200-400 UI/día), tiazidas (25 mg/día) y kinesioterapia. Se obtuvo una rápida disminución del dolor y la paciente se movilizó por sus propios medios. Se discuten estas indicaciones en el marco de los conocimientos actuales sobre enfermedades metabólicas del hueso.

Avaliaçäo histométrica da açäo local da calcitonina de salmäo no processo de reparo ósseo: estudo em ratos / Histometrical evaluation of the local effects of salmon calcitonin on the bone healing process: a study in rats

Neste estudo avaliou-se histometricamente a açäo local da calcitonina de salmäo em defeitos ósseos provocados cirurgicamente em fêmur de ratos. As avaliaçöes foram feitas aos 7, 14 e 21 dias após o ato cirúrgico. Näo se observou diferenças estatísticas aos 7 dias, entretanto no período de 14 dias houve diferenças com maior formaçäo óssea no grupo tratado. No período de 21 dias, em ambos os grupos, näo foi possível diferenciar o tecido ósseo neoformado e o adjacente. os resultados demonstraram, que o efeito da calcitonina foi observado somente no início do processo de reparo dos defeitos ósseos criados cirurgicamente

Efecto de dosis bajas de calcitonina sobre la remodelación ósea en mujeres postmenopáusicas con alto recambio / Effects of low calcitonin doses on bone remodeling in postmenopausal women with high bone turnover rate

Background: Calcitonin is specially indicated for the treatment of osteoporosis in women that cannot receive estrogen replacement therapy or that have a high bone turnover rate. Aim: To study the effects of low intranasal calcitonin doses on bone remodeling in postmenopausal women with a high bone turnover. Patients and methods: Forty one healthy women aged 56 ñ 6 years old, with a mean lapse after menopause of 7.6 ñ 6.5 years and with a high bone turnover rate, evidenced by an urinary hydroxyproline (mg/dl)/creatinine (g/dl) ratio of 52.4 ñ 7.2, were studied. They were randomly assigned to receive 100 or 50 U/calcitonin thrice a week during 3 months or to a control group that received placebo. All received 500 mg/day calcium carbonate. Urinary hydroxyproline/creatinine ratio was measured a 0, 15, 30, 60 and 90 days. Plasma bone fraction of alkanine phosphatases was measured at 0, 30 and 90 days. Results: Initial urinary hydroxyproline/creatinine ratio and plasma bone fraction of alkanine phosphatases were similar in all study groups and there was no change in these parameters during the study period. Conclusions: Intranasal calcitonin in doses of 100 U thrice a week or less, does not modify accelerated bone turnover in postmenopausal women

Abordagem clínica e laboratorial do bócio uninodular sólido: vantagens da determinaçäo da calcitonina sérica por métodos distintos no rastreamento do carcinoma medular de tireóide, forma esporádica / Clinical and laboratorial approach of solid uninodular goiter: advantage of serum calcitonin determination by different methods in medullar thyroid carcinoma screening, sporadic form

A apresentação clínica mais freqüente da forma esporádica do carcinoma medular da tireóide (CMT) é o bócio uninodular sólido (BUS), apresentação esta semelhante aos demais tumores que afetam a glândula. O estabelecimento da freqüência de CMT em BUS apresenta implicações importantes não só diagnósticas, como também terapêuticas, visto a abordagem cirúrgica do CMT diferir de outros tumores tireoideanos. Para investigar a prevalência de CMT em BUS, dosamos calcitonina (CT) sérica, marcador bioquímico do CMT, por métodos distintos (RIA e IRMA) em 60 casos (55 mulheres; com idades entre 22 e 75 anos). A análise citológica obtida através de punção biópsia (PAAF) revelou 100 por cento de especificidade e 67 por cento de sensibilidade na detecção de carcinoma de tireóide. Considerando-se o grau de suspeita clínica para neoplasia tireoideana e os achados anatomopatológicos, houve 60 por cento de correlação positiva. CMT foi diagnosticado através da elevação da CT sérica em um dos 59 casos (1,69 por cento) e confirmado posteriormente pela PAAF e anatomopatológico. A incidência de CMT entre os casos de neoplasias tireoideanas nesta amostra foi de 12,5 por cento (1/8). Concluímos que a dosagem rotineira da CT sérica em casos com BUS não só complementa o estudo desta doença, como auxilia fortemente no diagnóstico do CMT. Tanto o IRMA como o RIA mostraram-se métodos úteis no rastreamento do CMT. Entretanto, o RIA pode provavelmente detectar ainda mais precocemente a elevação de formas não monoméricas da molécula de CT, as quais nos casos de CMT são usualmente mais abundantes que as formas monoméricas.

Histological evaluation of the calcitonin effects on bone healing following titanium implant insertion / Avaliaçäo histológica dos efeitos da calcitonina na reparaçäo óssea após a colocaçäo de implante de titânio

O objetivo deste estudo foi foi

Efeito da calcitonina de salmäo sobre a cicatrizaçäo de defeitos ósseos: estudo radiográfico e histológico em coelhos / Effect of calcitonin on bone healing process of cincumscribed bone defects: histological and radiographic analysis

O objetivo deste estudo foi avaliar, histológica e radiograficamente, a açäo da calcitonina de salmäo sobre a cicatrizaçäo de defeitos ósseos circunscritos, criados cirurgicamente em fêmur de coelhos saudáveis. Esses foram divididos aleatoriamente em dois grupos: controle (n = 12) e tratado (n = 12). O grupo controle näo recebeu qualquer substância durante o experimento, enquanto no grupo tratado foi aplicada dose diária de 2 Ul/kg de calcitonina por via intramuscular. Os animais foram sacrificados nos períodos de 7, 14, 21 ou 28 dias após a criaçäo dos defeitos ósseos. As áreas radiolúcidas desses foram medidas em mm2, por meio de um programa de computador denominado Auto-CAD, demonstrando que essas, em média, foram menores no grupo tratado, mas estatisticamente significantes apenas nos períodos intermediários de 14 e 21 dias. Histologicamente, aos 7 dias, os defeitos do grupo tratado apresentaram uma maior neoformaçäo óssea. Aos 28 dias, houve a formaçäo de um osso menos compacto no grupo controle. No entanto, aos 14 e 21 dias, os resultados foram semelhantes entre os dois grupos. Os resultados obtidos neste trabalho possibilitaram inferir que a calcitonina de salmäo demonstrou resultados positivos quanto à cicatrizaçäo óssea em defeitos circunscritos, baseados nas análises radiográficas e histológicas realizadas

Algoritmo para el tratamiento de la osteoporosis / Algorythm for treatment of osteoporosis

La osteoporosis es un padecimiento por disminución de la masa ósea por unidad de volumen, que compromete la competencia mecánica del esqueleto. Es debida a aumento de reabsorción ósea, a disminución de la formación de hueso o a una combinación de ambos procesos. Es inducida por múltiples factores. Su tratamiento involucra un proceso diagnóstico que determina primero la pérdida del componente óseo mineral y después el tipo de alteración del remodelamiento. A partir de esto, se decide el tipo de tratamiento a seguir, ya sea con formadores de hueso o con anti-reabsorbentes