Osteoporose na artrite reumatoide: papel do sistema vitamina D/hormônio paratireóideo / Osteoporosis in rheumatoid arthritis: role of the vitamin D/parathyroid hormone system

A osteoporose é uma característica extra-articular bem estabelecida da artrite reumatoide (AR). A inflamação sistêmica parece ser essencial para causar uma alteração em múltiplos sistemas homeostáticos implicados na saúde óssea, como as vias RANK/RANKL/osteoprotegerina e Wnt/β catenina; vários outros fatores causais têm sido implicados, como o uso crônico de corticosteroides. Como a vitamina D exerce funções imunorreguladoras importantes, tem-se afirmado que o desarranjo do sistema vitamina D/hormônio paratireóideo (HPT), um determinante bem conhecido da saúde óssea, pode desempenhar um papel patogênico na autoimunidade; estudos com animais e dados clínicos apoiam essa hipótese. Além disso, os pacientes com AR parecem ser relativamente refratários à supressão de HPT induzida pela vitamina D. Portanto, a ligação entre a AR e a osteoporose pode ser em parte causada por alterações no sistema vitamina D/HPT. Uma melhor compreensão da fisiopatologia desse sistema pode ser crucial para prevenir e curar a osteoporose em pacientes com doenças inflamatórias/autoimunes. A maior evidência da correlação clínica de cooperação e interdependência entre a vitamina D e o HPT é que a correção da deficiência de vitamina D, pelo menos nas doenças autoimunes, deve ser orientada para a supressão do HPT.

Osteoporosis is a well-established extra-articular feature of rheumatoid arthritis (RA). Systemic inflammation seems to play a crucial role in causing an alteration of multiple homeostatic systems implied in bone health, such as the RANK/RANKL/Osteoprotegerin and Wnt/β catenin pathways; several other causal factors have been called into question, including the chronic use of corticosteroids. Since vitamin D exerts important immune-regulatory roles, it has been claimed that derangement of the vitamin D/parathyroid hormone (PTH) system, a well-known determinant of bone health, may play a pathogenic role in autoimmunity; animal models and clinical data support this hypothesis. Furthermore, RA patients seem to be relatively refractory to vitamin D-induced PTH suppression. Therefore, the link between RA and osteoporosis might in part be due to alterations in the vitamin D/PTH system. A better understanding of the pathophysiology of this system may be crucial to prevent and cure osteoporosis in patients with inflammatory/autoimmune diseases. A major clinical correlate of the strict cooperation and interdependence between vitamin D and PTH is that correction of the vitamin D deficiency, at least in autoimmune diseases, should be targeted to PTH suppression.

Vitamina D: ações extraósseas e uso racional / Vitamin D: non-skeletal actions and rational use

O número de dosagens do nível sérico de vitamina D tem apresentado crescimento muito expressivo nos últimos anos em todo o mundo. No Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo houve aumento de cerca de 700% em quatro anos nas solicitações desse hormônio. No entanto, há controvérsias na literatura sobre a real utilidade de sua dosagem e/ou suplementação, exceto em situações diretamente relacionadas ao metabolismo ósseo. No presente trabalho são revistos o metabolismo, as fontes e as ações da vitamina D no organismo. Estudos observacionais, ensaios clínicos, revisões sistemáticas e metanálises, cujo foco é a relação entre vitamina D e doenças ou condições clínicas, como câncer, doenças cardiovasculares, diabetes e quedas, foram pesquisados na literatura, analisados e discutidos. Os resultados estão apresentados em forma de perguntas e respostas, tabelas e figura. Discute-se o papel da vitamina D em todas essas situações, e salientam-se os pontos controvertidos.

Recent years have witnessed a substantial increase in the number of seric determinations of vitamin D, in aworldwide basis. At Hospital das Clínicas of Faculdade de Medicina of Universidade de São Paulo that increase reached 700% over the last four years. Nevertheless there are many controversies on the literature about the role of vitamin D in conditions unrelated to themusculoskeletal system. In this study the metabolism, sources and actions of vitamin D on the body are reviewed. Observational studies, clinical trials, systematic reviews and metanalysis which focused on the relationship between the vitamin and conditions such as cancer, cardiovascular disease, diabetes and falls were searched on the literature, analyzed and discussed. Results are presented as quiz and answer, tables and a figure. The role of vitamin D on the above-mentioned conditions is discussed, and the controversial issues stressed.

Hipocalcemia: complicación en cirugía endocrino-metabólica: a propósito de un caso / Hypocalcemia: complication in surgery endrocrine-metabolica: a purpose of a case

La hipocalcemia es una complicación metabólica común en la tiroidectomía total y en el bypass gástrico. El mecanismo que la provoca es diferente en ambas entidades clínicas. La incidencia de esta complicación es variable, la presentación clínica es inespecífica y el manejo farmacológico no está estandarizado. Se presenta el caso clínico de una paciente de 40 años, a la cual se le realizaron ambas cirugías con el desarrollo de hipocalcemia sintomática post-operatoria.

Hypocalcemia is a common metabolic complications in total thyroidectomy and gastric bypass. The mechanism that causes it is different in both clinical entities. The incidence of this complication is variable, the clinical presentation is nonspecific and pharmacological management is not standardized. A case report of a patient of 40 years which were performed both surgeries with the development of postoperative symptomatic hypocalcemia.

Distúrbios do eixo cálcio-PTH-vitamina D nas doenças hepáticas crônicas / Disturbances of calcium-PTH-vitamin D axis in chronic liver diseases

Distúrbios no eixo cálcio-PTH-vitamina D são freqüentemente associados às doenças hepáticas crônicas (DHC). Já foi demonstrado que pacientes com DHC apresentam uma tendência à diminuição do cálcio e vitamina D, com aumento compensatório do PTH. Embora a diminuição da hidroxilação da vitamina D em 25 (OH) vitamina D fosse considerada o mecanismo principal destas alterações, estudos recentes vêm demonstrando que, mesmo nos estágios avançados de doença, o fígado ainda consegue manter níveis adequados de 25 (OH) vitamina D. Desta forma, outros fatores (ex: dieta inadequada, diminuição da exposição à luz solar) seriam os responsáveis pelas alterações no eixo cálcio-PTH-vitamina D. Além disso, o tratamento das DHC com glicocorticóides (fibrose cística) e ribavirina (Hepatite C) parece contribuir como agravante destes distúrbios. Por outro lado, parece ser a osteoporose, e não a osteomalácia ou o hiperparatireoidismo secundário, a principal alteração nas DHC. Assim, continua objeto de discussão o papel das alterações do eixo cálcio-PTH-vitamina D na osteodistrofia hepática.

Osteodistrofia hereditaria de Albright (pseudohipoparatiroidismo, pseudopseudohipoparatiroidismo). Reporte de un caso / Albright hereditary osteodystrophy (pseudohypoparatiroidism). Report of a case

En el presente trabajo se hace una revisión de la literatura del síndrome de osteodistrofia hereditaria de Albright, así como el reporte de un caso detectado en la consulta de la Maestría de Estomatología Pediátrica de la Universidad Autónoma de San Luis Potosí

An update on the discovery, pathophysiological actions, clinical manifestations and possible physiology of parathyroid related peptide

PTHrP has had an unidentified role in medicine since 1930, when Albright described a patient with renal cortical cell carcinoma with hypercalcemia. Since then hypercalcemia has been recognized as the most common paraneoplastic syndrome. At that time the concept of ®ectopic PTH syndrome® was introduced, and remained in literature until the true etiology was finally described. In the early 1970's Roof and Benson presented evidence that PTH in humoral hypercalcemia differed from ®authentic® PTH. This marked the starting point for researchers to try identifying the molecule that mimicked PTH action and structure. This molecule, named parathyroid-related peptide, has been associated to hypercalcemia seen with solid tumors, such as squamous cell carcinoma of the lung and renal cortical cell carcinoma. PTHrP has been demonstrated to have similar actions to PTH but to differ in decreasing osteoblastic activity while increasing osteoclastic activity. The more fascinating finding was the presence of the PTHrP genes throughout the body, mostly the lactating breast as well as the heart, lungs and skin among others. Despite its identification, finding its physiological roles on normal tissue still remains to be clarified

Peripheral neuroendocrinology of the cervical autonomic nervous system

1. The sympathetic superior cervical ganglia (SCG) provide innervation to the pineal gland and median eminence through the internal carotid nerve and to the thyroid and parathyroid glands through the external carotid nerve. 2. Postsynaptic activation in median eminence nerve endings shortly after superior cervical ganglionectomy (SCGx) was accompanied by a depression of LH and FSH release and by a 3-5 day delay in rat estrous cyclicity. A decrease in TSH and GH release and an increase in ACTH and prolactin release were also found. These effects were accompanied by a) an increase in medial basal hypothalamic (MBH) LHRH, TRH and GHRH, b) a decrease in MBH somatostatin, AVP and CRH, and c) a normal adenohypophyseal response to hypophysiotropic hormones. Neurohypophyseal AVP release decreased during degeneration of sympathetic nerve terminals in the neurohypophyseal lobe after SCGx. The effects were generally mediated by alpha 1-adrenoceptors and were pineal gland. 3. In thyroid and parathyroid tissue the following events were observed during the wallerian degeneration phase after SCGx: a) alpha 1-adrenoceptor inhibition of thyroxine (T4) release, b) alpha 1-adrenoceptor inhibition, together with beta-adrenoceptor stimulation, of calcitonin release, and c) alpha 1-adrenoceptor inhibition of parathyroid hormone release. Thyroid sympathetic nerves also modulate slow phenomena such as compensatory thyroid growth after partial thyroidectomy. 4. In rats subjected to cholinergic decentralization of the thyroid gland, a decrease of plasma T4 and an increase of plasma TSH, as well as an impaired goitrogenic and thyroid compensatory response were detectable. The calcitonin and PTH response to changes in calcium levels increased after regional parasympathetic denervation. 5. The results indicate that cervical autonomic nerves constitute a parallel pathway through which the brain communicates with the endocrine system

Metabolismo del hueso periodontal: Parte III. Control sistémico del metabolismo de hueso / Periodontal bone metabolism: Part III. Systemic control of bone metabolism

El presente trabajo es el tercero de una serie de 5 artículos dedicados al estudio del metabolismo del hueso periodontal. En los dos primeros se hizo una descripción de la biología celular del hueso periodontal y de los fenómenos fisiológicos que se encadenan en el ciclo de remodelado óseo. El objetivo del presente trabajo es presentar una revisión actualizada del control sistémico del metabolismo de hueso. A nivel sistémico, tres hormonas principales inciden en el metabolismo del hueso periodontal: la paratohormona (PHT), la calcitonina (CT) y el metabolito activo de la vitamina D3 (1,25-dihydroxivitamina D3). La primera y la tercera tienen una acción semejante y sinérgica que está dirigida a la estimulación de la reabsorción ósea. La CT, por el contrario, tiene un efecto antagónico, ya que inhibe la función osteoclástica. Las próximas entregas tratarán acerca del control local del metabolismo óseo, así como del comportamiento del hueso periodontal en salud y enfermedad

Phosphorus and Calcium Homeostasis in Chronic Subtotally Nephrectomized Parathyroidectomized Rats

Calcium and phosphorus balance studies were carried out in subtotally nephrectomized rats (NX), with or without parathyroidectomy (NX-PTX; NX sham-PTX) in order to determine the ability of the remnant kidney to regulate excretion of these elements in the absence of parathyroid hormone. The rats were fed three different phosphorus diets, and calcium intake was also varied. We found that the NX-PTX rats adapted to the three different phosphorus diets in a manner indistinguishable from the NX sham-PTX rats. The per cent of ingested phosphorus excreted in the urine increased as dietary phosphorus increased. When supplementary calcium was added to the diet urinary phosphorus excretion fell and fecal phosphorus increased, in an identical fashion in the NX-PTX and NX sham-PTX animals. Urinary calcium excretion decreased as dietary phosphorus increased, and UCaV increased when supplementary calcium was provided in the diet. Total body calcium and phosphorus balance (intake-(urine+feces)) varied with intake, but was not significantly different between the NX-PTX and NX sham-PTX rats. These experiments demonstrate that subtotally nephrectomized rat have a parathyroid-independent mechanism(s) for regulating both urinary and fecal calcium and phosphorus excretion. The mechanism is not revealed by the present study, but may relate to changes in serum calcium and/or phosphorus which occur following parathyroidectomy.