Effect of Alendronate on Vascular Calcification in CKD Stages 3 and 4: A Pilot Randomized Controlled Trial

Abstract

Vascular calcification contributes to cardiovascular disease in patients with chronic kidney disease (CKD). Few studies have addressed interventions to decrease vascular calcification; however, experimental studies report benefits of bisphosphonates. Recent studies of hemodialysis patients also suggest benefits of bisphosphonates on vascular calcification; however, no study exists in nondialysis patients with CKD. We conducted a randomized controlled trial to determine the effect of bisphosphonates on vascular calcification in patients with CKD. 51 patients with CKD stages 3-4 were recruited from a hospital outpatient setting; 50 were treated with study medication. Patients were randomly assigned to either alendronate, 70 mg (n = 25), or matching placebo (n = 25), administered weekly. The primary outcome was change in aortic vascular calcification after 18 months. Secondary outcomes included superficial femoral artery vascular calcification, arterial compliance, bone mineral density (BMD), renal function, and serum markers of mineral metabolism. At baseline and 12 and 18 months, computed tomography, pulse wave velocity using SphygmoCor (AtCor Medical, PWV Inc, www.atcormedical.com), and dual-energy x-ray absorptiometry were performed to measure vascular calcification, arterial compliance, and BMD, respectively. Analysis was by intention to treat, with a random-effect linear regression model to assess differences. 46 patients completed the study (24 alendronate, 22 placebo); baseline mean age was 63.1 +/- 1.8 years, estimated glomerular filtration rate was 34.5 +/- 1.4 mL/min/1.73 m(2), 59% had diabetes, and 65% were men. 91% had aortic vascular calcification at the start and 78% showed progression. At 18 months, there was no difference in vascular calcification progression with alendronate compared with placebo (adjusted difference, -24.2 Hounsfield units [95% CI, -77.0 to 28.6]; P = 0.4). There was an increase in lumbar spine BMD (T score difference, +0.3 [95% CI, 0.03-0.6]; P = 0.04) and a trend toward better pulse wave velocity (-1 m/s [95% CI, -2.1 to 0.1]; P = 0.07) with alendronate. Femoral BMD was similar between groups. There was a nonsignificant decrease in kidney function in patients on alendronate therapy compared with placebo (-1.2 mL/min/1.73 m(2) [95% CI, -4.0 to 1.7]). Small sample size and baseline differences, especially with aortic vascular calcification, may have diminished any potential difference between groups. Unlike previous studies of hemodialysis patients, alendronate did not decrease the progression of vascular calcification compared with placebo in patients with CKD during 18 months.