The parathyroid-bone axis in uremia: new insights into old questions.
In recent years, considerable progress has been made in our understanding of the pathophysiology of secondary hyperparathyroidism in chronic renal failure and the contribution of the level of circulating parathyroid hormone to the genesis of the various types of uremic bone disease. A better insight into the cellular and molecular basis of abnormal parathyroid hormone secretion has been obtained; in particular the abnormal expression of the receptors for calcium and vitamin D in the hyperplastic parathyroid tissue, the demonstration of a direct enhancing effect of extracellular phosphate on parathyroid hormone secretion, the involvement of abnormally expressed growth factors such as transforming growth factor-alpha in parathyroid hyperplasia, and the occurrence of monoclonal parathyroid cell growth, which is probably responsible for the eventual development of autonomous hyperparathyroidism. In the pathogenesis of osteitis fibrosa, a synergistic action of parathyroid hormone with cytokines and growth factors is highly probable from a theoretical point of view, and personal preliminary observations support this hypothesis. The relative importance of metabolic acidosis is controversial. The existence of a skeletal resistance to parathyroid hormone in chronic renal failure could be partly as a result of a down-regulation of the parathyroid hormone/parathyroid hormone-related peptide receptor. In the presence of normal or only slightly elevated plasma intact parathyroid hormone levels, this may favour the development of adynamic bone disease. Finally, in terms of clinical practice the non-invasive diagnosis of the precise type of renal osteodystrophy will require the introduction of recently developed, more accurate plasma markers of bone formation and resorption, in addition to plasma intact parathyroid hormone.
Hory
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Unité 90 de l'INSERM, Hôpital Necker, Paris, France.
Drüeke
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TB
D000818:Animals; D001842:Bone and Bones / Q000503:physiopathology*; D006801:Humans; D010280:Parathyroid Glands / Q000503:physiopathology*; D010281:Parathyroid Hormone / Q000378:metabolism; D014511:Uremia / Q000503:physiopathology*
D010281:Parathyroid Hormone