In patients with
chronic kidney disease (CKD) or those undergoing
hemodialysis, pathological calcific deposition known as ectopic calcification occurs in soft tissue, resulting in a life-threatening disorder. A potent and effective inhibitor of ectopic calcification is eagerly expected. In the current study, the effects of
FYB-931, a novel
bisphosphonate compound synthesized for the prevention of ectopic calcification, were compared with those of
etidronate using both in vitro and in vivo models. In vitro,
FYB-931 inhibited calcification of human aortic smooth muscle cells induced by high
phosphate medium in a concentration-dependent manner, and the effect was slightly more potent than that of
etidronate. In vivo, rats were administered with three
subcutaneous injections of
vitamin D3 to induce
vascular calcification, and were given
FYB-931 (1.5, 5, or 10 mg/kg) or
etidronate (9, 30, or 60 mg/kg) orally once daily for 14 days. The increased aortic
phosphorus content as an index of
vascular calcification was inhibited by both
FYB-931 and
etidronate in a dose-dependent manner; however,
FYB-931 was 10 times more potent than
etidronate.
FYB-931 inhibited serum
tartrate-resistant acid phosphatase (
TRACP) activity as a
bone resorption marker 5.2 times more potently than
etidronate.
FYB-931, but not
etidronate, significantly decreased serum
phosphorus levels. The preferential inhibition of aortic calcification by
FYB-931 suggested that possible additional effect including a decline in serum
phosphorus may lead to an advantage in terms of its efficacy.