Calcif Tissue Int. 2025 Dec 1;116(1):139. doi: 10.1007/s00223-025-01448-9.
ABSTRACT
Hyperphosphatemia is a common complication of chronic kidney disease (CKD) and occurs in both high- and low-turnover bone disorders. While phosphate (P) control is known to reduce adverse effects, most supporting studies have focused on high-turnover models. This study evaluates the effects of two P binders-calcium carbonate (CaCO₃) and sevelamer carbonate-on laboratorial markers and bone histomorphometry in a low-turnover bone disease model. Wistar rats underwent 5/6 nephrectomy and total parathyroidectomy (Nx + PTx) to induce low-turnover bone disease. Animals were assigned to 4 groups: Sham, untreated Nx + PTx, Nx + PTx + CaCO₃, and Nx + PTx + sevelamer. After 8 weeks, we performed biochemical analysis, bone histomorphometry, gene expression (SOST, β-catenin, DKK-1), immunohistochemistry (sclerostin, β-catenin, FGF23, DKK-1), and apoptosis assays. Bone histology confirmed low-turnover disease in Nx + PTx rats, which also developed CKD and hyperphosphatemia. Both P binders effectively reduced serum P levels, but only CaCO₃ corrected hypocalcemia. Notably, CaCO₃ treatment led to increased osteoid parameters, elevated osteoblast surface and absence of tetracycline labeling - hallmarks of osteomalacia. Moreover, CaCO₃ increased osteoblast apoptosis. In a rat model of low-turnover bone disease with normal dietary P, high-dose CaCO₃ impaired bone mineralization and induced osteomalacia. These findings highlight potential risks of calcium-based phosphate binders in patients with low bone turnover and hyperphosphatemia, supporting the need for careful clinical consideration and monitoring.
PMID:41326783 | DOI:10.1007/s00223-025-01448-9