Fisiopatologia da osteoporose induzida por glicocorticóide

Abstract

RESUMOO hipercortisolismo crônico é a causa mais freqüente de osteoporose secundária, acometendo principalmente o osso trabecular. Aproximadamente 30-35% dos pacientes com síndrome de Cushing apresentam fraturas de vértebras por compressão e o risco de fraturas de colo de fêmur é aumentado em 50% nessa população. Vários mecanismos têm sido propostos para explicar a ocorrência de osteoporose nessa condição, como a ação direta dos glicocorticóides nas paratireóides e nas células ósseas, alterações na produção de prostaglandinas, citocinas, interleucinas, alterações na secreção do hormônio do crescimento (GH), do fator insulina símile-I (IGF-I) e esteróides gonadais. Resultados controversos têm sido apresentados quanto à alteração na secreção do PTH nesta situação, onde níveis normais e elevados têm sido descritos. A elevação da secreção de PTH pode ser secundária a distúr -bios do metabolismo mineral induzidos pelo hipercortisolismo, como diminuição na absorção intestinal, aumento da excreção renal de cál -cio, diminuição no número de receptores paratireoideanos para a 1,25(OH) 2 D 3 , anormalidades no limiar de sensibilidade do cálcio ( set point ) para a secreção do PTH e alteração na sua atividade. Nesta revisão, são discutidos diversos aspectos fisiopatológicos e possíveis mecanismos envolvidos na associação entre hipercortisolismo e osteoporose. Chronic hypercortisolism is the most frequent cause of secondary osteoporosis involving mainly trabecular bone. Approximately 30-35% of the patients with Cushing's syndrome present with compression fractures of vertebrae, and the risk of femoral neck fracture is increased in 50% in that population. Several mechanisms have been proposed to explain the association between hypercortisolism and osteoporosis, as the direct action of glucocorticoids in parathyroid glands and bone cells, alterations in the production of prostaglandins, citokines, interleukines, growth hormone (GH), insulin like growth factor I (IGF-I) and gonadal steroids. Contradictory results have been presented in relation to PTH secretion, where normal and high levels have been described. Elevated PTH secretion can occur as a consequence of disturbances in mineral metabolism, i.e. decrease in the intestinal absortion and elevation in the renal excretion of calcium, decrease in the number of parathyroid receptors for 1,25(OH) 2 D 3 , abnormalities in the calcium set point for PTH secretion, and alteration in PTH activity. In this review, several pathophysiologic aspects and possible mechanisms involved in the association between osteoporosis and hypercortisolism are discussed. (Arq Bras Endocrinol Metab 2003;47/1: 9-18)

Allogeneic mesenchymal stem cells and xenogenic platelet rich plasma, associated or not, in the repair of bone failures in rabbits with secondary osteoporosis

“…The observed bone density varied between values below 1.375cm 3 and up to 1.465cm 3 , corresponding to the last and penultimate step of the penetrometer, respectively. Previous studies have described, in rabbits and mice, the predominant presence of fibrous connective tissue, associated with intense mixed inflammatory infiltration at the site of failure, in the first 30 days after bone failures in healthy or unhealthy patients 13,12 .…”

“…All the rabbits induced to hypercortisolism and osteoporosis presented average bone densities inferior to 1.37cm 3 , having the last step of lower density of the penetrometer as densitometric reference. In this respect, a limitation of the proposed method is identified when a penetrometer of only 11 steps is used, because it is not possible to accurately determine the values below this threshold.…”

“…penetrometer was used as a densitometric reference, as proposed by Louzada 18. According to this author, this technique presents high sensitivity, precision, reproducibility, fidelity, easy feasibility and low cost and is widely described by other researchers, especially applied to rabbits with induced osteoporosis 3 , which justifies its adoption in the methodology presented in this study.…”

“…However, phosphorus does not circulate in plasma bound to serum proteins, being fully filtered in the glomerulus and easily reabsorbed in the contorted tubules. During osteoporosis, parathyroid hormone binds to the enzyme adenyl cyclase, inhibiting the cotransport of phosphorus in the contorted tubules, inducing phosphaturia and allowing the reabsorbed calcium ions to not be reincorporated into the bone tissue 3 . Although the concentration of urinary phosphorus in the present study has not been evaluated, it is believed that this condition has occurred, corroborating for the presumption of success in the proposed model.…”

“…Chronic iatrogenic hypercortisolism is the most frequent cause of secondary osteoporosis, corresponding to 25% of the etiologies in humans 3 . According to these authors, glucocorticoids can induce parathyroid hyperplasia, with subsequent serum increase in parathyroid hormone levels (PTH), stimulating calcium reabsorption and release of calcium and phosphorus ions into the extracellular environment 4 .…”