NPS R-568 halts or reverses osteitis fibrosa in uremic rats

Osteitis fibrosa is a common bone injury associated with secondary hyperparathyroidism (2 degrees HPT). NPS R-568 is a phenylalkylamine derivative that acts as an agonist at the cell-surface Ca2+ receptor ("calcimimetic") and inhibits parathyroid hormone (PTH) secretion. Ln the present study, we tested whether NPS R-568 could ameliorate osteitis fibrosa in partially nephrectomized (Nx) rats with 2 degrees HPT. Six months after surgery, Nx rats had developed mild but progressive 2 degrees HPT and osteitis fibrosa. Two groups of Nx rats received NPS R-568 (3 and 30 mg/kg body wt.day) by daily gavage for 30 days, which led to a dose-related decrease in serum PTH levels and to a marked reduction in peritrabecular fibrosis (0.96 +/- 0.49% to < 0.1%). Furthermore, 2 degrees HPT was associated with decreases in volumetric cortical bone mineral density (vCtBMD) and in cortical bone stiffness at the femoral midshaft. NPS R-568 significantly restored the deficits in vCtBMD and stiffness. These results indicate that NPS R-568 has beneficial effects on bones with osteitis fibrosa by normalizing serum PTH levels.