Prevention of aortic calcification by etidronate in the renal failure rat model.

Our recent clinical study indicated that etidronate may inhibit the progression of aortic calcification in hemodialysis patients. To determine whether etidronate inhibits aortic calcification in renal failure rats, renal failure was induced by subtotal nephrectomy, in which 5/6 of the kidneys were removed. Significant increases in serum creatinine levels were observed 2 weeks after the operation, at which point treatment with etidronate and calcitriol was initiated. Etidronate at 5 or 10 mg/kg significantly reduced the thoracic and abdominal aortic calcification induced by calcitriol. It also reduced the dysfunction in aortic contraction. The elevation of bone metabolism and reduction of bone mineral density observed in the nephrectomized rats were not affected by treatment with 5 mg/kg etidronate. No changes in serum Ca and the product of Ca and P levels were observed between the non etidronate-treated group and the 5 mg/kg etidronate-treated group. Moreover, the reduction in the aortic expression of matrix Gla protein mRNA observed in nephrectomized rats was reversed by 5 mg/kg etidronate. These results show that etidronate at concentrations that do not affect the bone mineral density inhibits aortic calcification and recovers vascular dysfunction in renal failure rats.

Inhibition of the progression of aortic calcification by etidronate treatment in hemodialysis patients: long-term effects.

To confirm the inhibitory effect of etidronate on the progression of vascular calcification (VC), 21 patients were randomly enrolled. All 21 patients had end-stage renal disease and were undergoing hemodialysis (HD) three times per week. Patients were observed clinically for 12 months before etidronate treatment and then etidronate was given orally just prior to sleep on the days of dialysis for 23 months. The aortic calcification area (ACA) increased significantly during the 12 months before etidronate treatment. While the ACA of the drug-treated group did not change 12 and 23 months after the initiation of etidronate treatment, the ACA in the control group was significantly elevated 23 months later. These results strongly indicate that etidronate inhibits the progression of VC. Bone mineral density did not change during etidronate treatment. Our findings suggest that etidronate might effectively protect against progressive VC in HD patients.

Inhibitory effects of etidronate on the progression of vascular calcification in hemodialysis patients.

The present study was designed to determine if etidronate inhibits the development of aortic calcification in hemodialysis (HD) patients. Eighteen Japanese HD patients were divided randomly into etidronate-treated or control groups. Etidronate was given orally at the dose of 200 mg just before sleep on the day of dialysis, which was performed three times per week. In the control group, the aortic calcification area (ACA) increased after 6 months. In the patients who received etidronate, however, when compared to the control group, increases in ACA were significantly suppressed. Serum Ca, P, and the Ca x P product did not change during etidronate treatment. These results suggest that etidronate inhibits the progression of vascular calcification without changes in serum Ca and P levels.

[Suppressive effects of bisphosphonates on the vascular calcification in ESRD patients].

The progress of aortic calcification is associated with the incidence of cardiac and cerebrovascular diseases in hemodialysis patients. The present study was designed to determine whether etidronate can affect the development of aortic calcification in hemodialysis patients. Etidronate was given orally just before sleep on the day of dialysis, which was performed 2 or 3 sessions per week. Aortic calcification area (ACA), bone mineral density (BMD), and biochemical parameters were measured 6 months after the start of etidronate treatment to them compare with control. ACA in the control group showed a statistically significant increase after 6 months. However, the patients who received etidronate had no significant changes in ACA. Clinical and biochemical parameters and BMD were not influenced by etidronate treatment except serum alkaline phosphatase. These results suggest that etidronate has a potential ability to inhibit the progression of vascular calcification in hemodialysis patients, and that this beneficial effect of etidronate may prevent cardiovascular and cerebrovascular diseases that are major causes of death in hemodialysis patients.

Effect of etidronate on aortic calcification and bone metabolism in calcitriol-treated rats with subtotal nephrectomy.

The present study was undertaken to determine the effects of etidronate (ED) on calcitriol-induced aortic calcification and bone metabolism in rats with renal failure. Severe aortic calcification was induced by treatment with calcitriol for 3 weeks in rats in which 5/6 of the kidneys were removed (SNx group). Treatment of ED (10 mg/kg) together with calcitriol after subtotal nephrectomy (SNx) significantly inhibited thoracic and abdominal aortic calcification 3 weeks after the operation; however, ED (2 mg/kg) was ineffective. The serum levels of osteocalcin and pyridinoline decreased in ED (10 mg/kg) treated-renal failure rats compared with SNx rats. Total bone mineral density (BMD) in the SNx group was lower than that in the sham group, in which animals were treated with calcitriol after a sham operation. The total BMD value in the ED (10 mg/kg)-treated group was similar to that in the SNx group, whereas the levels of cancellous BMD were low in the ED (10 mg/kg)-treated rats. Our data show that ED at a dosage that suppresses bone metabolism markedly inhibits vascular calcification in rats with renal failure.