Effects of cyclic intermittent etidronate therapy on coronary artery calcification in patients receiving long-term hemodialysis.
BACKGROUND
Coronary artery calcification (CAC) is thought to be associated with greater cardiovascular mortality in patients with end-stage renal disease than in nonuremic persons. The purpose of the present study is to assess the effects of etidronate, a synthetic analogue of pyrophosphate, on progression of CAC score.


METHODS
The extent of CAC was evaluated by using multidetector spiral computed tomography. Repeated CAC score estimation was possible in 35 patients (29 men, 6 women). Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry. Serum osteoprotegerin (OPG) was measured by using enzyme-linked immunoassay. Serum etidronate was measured by means of the gas spectrometry technique using deuterium-labeled etidronate as internal standard.


RESULTS
Mean patient age was 63.2 +/- 8.2 (SD) years, and mean duration of dialysis therapy was 7.4 +/- 5.5 years. CAC score was estimated 3 times in each patient. After the second CAC score estimation, 35 patients were administered etidronate, 200 mg/d, for 14 days. This cycle was repeated 3 times every 90 days. CAC progression was significantly less pronounced during treatment with etidronate compared with the period before treatment was initiated. The median annualized absolute increase in calcified volume was 195.0 mm3 without treatment compared with -490.0 mm3 during treatment ( P < 0.01). Patients were divided into 2 groups based on changes in CAC score during etidronate treatment. Responders (n = 26) were patients whose CAC score decreased during therapy, and nonresponders (n = 9) were patients whose CAC score increased, even after etidronate therapy. Serum C-reactive protein values (0.18 +/- 0.13 mg/dL) in the responder group were greater than those (0.14 +/- 0.08 mg/dL) in the nonresponder group ( P = 0.013). Serum OPG levels decreased significantly during etidronate therapy (256.8 +/- 93.8 versus 245.0 +/- 83.0 pg/mL; P = 0.0161). Etidronate was well tolerated during the study. BMD values during etidronate therapy were not significantly changed from 0.941 +/- 0.125 to 0.968 +/- 0.246 g/cm2.


CONCLUSIONS
Results of the present study suggest that the extent of CAC may be suppressed by etidronate in association with a reduction in chronic inflammatory responses. They also suggest that a decrease in serum OPG concentrations by means of etidronate may be associated with changes in vascular calcification in dialysis patients.
Nitta
Kosaku
K
Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan. nitta@kc.twmu.ac.jp
Akiba
Takashi
T
Suzuki
Koichi
K
Uchida
Keiko
K
Watanabe
Ryo-Ichiro
R
Majima
Kazuhiro
K
Aoki
Takanao
T
Nihei
Hiroshi
H
D000368:Aged; D001774:Blood Chemical Analysis; D015519:Bone Density; D023921:Coronary Stenosis / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology; D012968:Etidronic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood; D018124:Receptors, Tumor Necrosis Factor; D006435:Renal Dialysis; D036542:Tomography, Spiral Computed
D006023:Glycoproteins; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human; D012968:Etidronic Acid