Denosumab, alendronic acid show null effect on aortic valve calcification
Both denosumab and alendronic acid fall short of reducing disease progression in patients with calcific aortic stenosis, a study has shown.
A total of 150 patients (mean age 72 years, 21 percent female) with peak aortic jet velocity of 3.36 m/s were randomized to receive denosumab (60 mg every 6 months; n=49), placebo injection (n=25), alendronic acid (70 mg once weekly; n=51), or placebo capsule (n=25).
All patients underwent serial assessments with Doppler echocardiography, computed tomography aortic valve calcium scoring, and 18F-sodium fluoride positron emission tomography and computed tomography.
At baseline, aortic valve calcium score of the population was 1,152 Agatston units (AU). The primary endpoint of the 24-month change in aortic valve calcium score did not significantly differ between denosumab and placebo (median, 343 vs 354 AU; p=0.41), or between alendronic acid and placebo (median, 326 vs 354 AU; p=0.49).
The same was true for changes in peak aortic jet velocity or 18F-sodium fluoride aortic valve uptake.
Serum C-terminal telopeptide levels, a measure of bone turnover, decreased by half from baseline to 6 months with denosumab (from 0.23 to 0.11 µg/L) and alendronic acid (from 0.20 to 0.09 µg/L) but remained the same with placebo (from 0.23 to 0.26 µg/L).
In light of the findings, alternative pathways and mechanisms need to be explored to identify disease-modifying therapies for the growing population of patients with calcific aortic stenosis.