Do calcimimetics directly alter bone remodeling?

摘要

Secondary hyperparathyroidism is an almost inevitable consequence of untreated chronic kidney disease (CKD), resulting in disordered skeletal remodeling and mineralization defects. Thus, due to the high circulating levels of parathyroid hormone (pTH), both osteoblast and osteoclast surfaces may be augmented and ultimately bone volume may be reduced (11). in CKD, synthesis of 1,25 dihydroxyvitamin D [1,25(OH)2D] is impaired. This occurs at least in part due to suppression of renal 25-hydroxyvitamin D-1a-hydroxylase [the enzyme synthesizing 1,25(oH)2D] by retained phosphate and by elevated concentrations of FGF23 (16), and in part because of loss of renal parenchyma. As a consequence, low levels of 1,25(oH)2D develop in stage 3 CKD leading to reduced calcium absorption (1). The low 1,25(OH)2D and resultant hypocalcemia can lead to the development of secondary hyperparathyroidism mainly due to the fact that 1,25(oH)2D via the vitamin D receptor, and extracellular ionized calcium [Ca2+]e, by activating the calcium-sensing receptor (CaSR), coordinately regulates pTH biosynthesis and parathyroid cell growth. The CaSR is a G protein-coupled receptor that responds to [Ca2+]e in particular, but also to multiple extracellular cations (2). in addition to modulating parathyroid function, CaSR also regulates renal calcium reabsorption.