Calcimimetics and vitamin D sterols reduce serum parathyroid hormone (PTH) in patients
with secondary hyperparathyroidism receiving dialysis, a disease state associated
with parathyroid hyperplasia, vascular calcification, bone disease, and increased
mortality. The aim of this study was to determine the effects of the research calcimimetic
AMG 641 (Amgen, Inc., Thousand Oaks, CA) or calcitriol (Sigma Aldrich Corporation,
St. Louis, MO) on vascular calcification in a rodent model of progressive uremia with
accompanying secondary hyperparathyroidism induced by dietary adenine. Treatment effects
on parathyroid gland hyperplasia and bone loss were also investigated. Rats were treated
daily with vehicle, calcitriol (10 ng), AMG 641 (3 mg/kg), or no treatment during
the 4 week period the animals were fed adenine. The uremia-induced increases in serum
PTH levels were significantly attenuated by both AMG 641 (>90%) and calcitriol (approximately
50%). AMG 641 significantly reduced calcium-phosphorus product (CaxP) and significantly
attenuated the development of both parathyroid hyperplasia and vascular calcification.
In addition, AMG 641 prevented the defects in trabecular bone volume, trabecular number,
and bone mineralization, as well as increases in trabecular spacing in this rodent
model of secondary hyperparathyroidism. Calcitriol (10 ng/rat) decreased osteoid surface/bone
surface, but had no effects on other bone parameters, or parathyroid hyperplasia (likely
due to the lower PTH suppressive effect of calcitriol at the dose used in this study).
However, this dose of calcitriol significantly exacerbated vascular calcification.
These results suggest that calcimimetics can reduce the development of vascular calcification,
parathyroid hyperplasia and bone abnormalities associated with secondary hyperparathyroidism.