Abstract
BackgroundSclerostin is a paracrine acting factor, which is expressed in the osteocytes and articular chondrocytes. Sclerostin decreases the osteoblast-related bone formation through the inhibition of the Wnt/β-catenin pathway. Osteocytes also express the Calcium sensing receptor which is a target for cinacalcet. The aim of this study was to assess the influence of six-month cinacalcet treatment on plasma sclerostin concentration in hemodialysed patients with secondary hyperparathyroidism (sHPT).MethodsIn 58 hemodialysed patients with sHPT (PTH > 300 pg/ml) plasma sclerostin and serum PTH, calcium and phosphate concentrations were assessed before the first dose of cinacalcet and after 3 and 6 months of treatment.ResultsSerum PTH concentration decreased after 3 and 6 month of treatment from 1138 (931–1345) pg/ml to 772 (551–992) pg/ml and to 635 (430–839) pg/ml, respectively. Mean serum calcium and phosphate concentrations remained stable. Plasma sclerostin concentration increased after 3 and 6 months of treatment from 1.66 (1.35–1.96) ng/ml, to 1.77 (1.43–2.12) ng/ml and to 1.87 (1.50–2.25) ng/ml, respectively. In 42 patients with cinacalcet induced serum PTH decrease plasma sclerostin concentration increased after 3 and 6 months of treatment from 1.51 (1.19–1.84) ng/ml to 1.59 (1.29–1.89) ng/ml and to 1.75 (1.42–2.01) ng/ml, respectively. Contrary, in the 16 patients without cinacalcet induced serum PTH decrease plasma sclerostin concentration was stable. Plasma sclerostin concentrations correlated inversely with serum PTH concentrations at the baseline and also after 6 months of treatment.Conclusions1. In hemodialysed patients with secondary hyperparathyroidism treatment with cinacalcet increases plasma sclerostin concentration 2. This effect seems to be related to decrease of serum PTH concentration.
Highlights
Sclerostin is a paracrine acting factor, which is expressed in the osteocytes and articular chondrocytes
In every patient plasma sclerostin concentration and serum parathyroid hormone (PTH), calcium, and phosphate concentrations were assessed before the first dose of cinacalcet and after 3 and 6 months of treatment
Among 13 patients ruled out of the study 4 people died, 2 received kidney allograft, 2 patients discontinued the study because of permanent decrease of serum PTH concentration below 150 pg/ml, 2 underwent parathyroidectomy, one patient refused to continue the treatment due to paresthesia, one patient withdrew the consent for the study and one moved out and was lost to follow-up
Summary
Sclerostin is a paracrine acting factor, which is expressed in the osteocytes and articular chondrocytes. Sclerostin decreases the osteoblast-related bone formation through the inhibition of the Wnt/βcatenin pathway. Sclerostin is a 22 kDa protein which acts as a soluble inhibitor of the canonical Wnt/β-catenin pathway [1]. It is synthetized mostly by osteocytes as a product of SOST gene. There is growing evidence that the effects of parathyroid hormone (PTH) on bone may be, at least partially, mediated by sclerostin expression. Administration of exogenous PTH leads to the decrease of sclerostin expression in osteocytes of mice [7]. In humans an inverse relation between plasma sclerostin and serum PTH concentrations has been found [8]
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