Secondary hyperparathyroidism with marked parathyroid hyperplasia is the major type of renal osteodystrophy. In addition to classic stimuli for parathyroid hormone (PTH) such as decreased concentrations of ionized calcium and 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3), calcitriol), several mechanisms have been suggested. Those include decreased density of calcitriol and calcium-sensing receptors, as well as the direct action of phosphate. Skeletal resistance to PTH was initially recognized as a blunted calcaemic action of PTH, which has been considered another stimulus for PTH secretion. Once suppression of PTH became possible by newly developed therapeutic modalities, it has been shown that this background abnormality plays an important role in the development of adynamic bone disease in uraemic patients. However, the mechanism of skeletal resistance to PTH has not been fully elucidated yet, but recent papers suggested that osteoprotegerin (OPG) accumulating in uraemic serum might inhibit osteoclastogenesis induced by PTH.