Researchers at Nagoya University in Japan reported on Apr. 14 that common osteoporosis drugs could help slow or halt the progression of aortic aneurysms, a condition where the main artery carrying blood from the heart becomes abnormally enlarged. The findings were published in the Journal of Clinical Investigation.
Aortic aneurysms can be fatal if they rupture, and there are currently no effective drug therapies to stop their development. Surgery remains the only definitive treatment, with decisions based on imaging and assessment of rupture risk.
The research team found that clonal hematopoiesis—an age-related process where blood-forming stem cells acquire genetic mutations—is linked to faster growth of aortic aneurysms. In their clinical study involving 44 patients scheduled for surgery, about 60% had clonal hematopoiesis and showed significantly quicker expansion rates than those without it. The researchers said this marker could help predict which patients are at higher risk for rapid disease progression.
Using mouse models with Tet2 gene mutations associated with clonal hematopoiesis, scientists observed more rapid aneurysm growth and structural changes in the aorta compared to controls. They identified increased activity in osteoclast-like cells and highlighted the role of the RANK/RANKL signaling pathway—known from osteoporosis research—in driving these changes.
Treatment with anti-RANKL antibodies and alendronate, both commonly used for osteoporosis, significantly reduced aneurysm progression in mice. Assistant Professor Yoshimitsu Yura said: "Our hypothesis that vascular diseases may result from blood aging enabled us to identify a mechanism underlying aortic aneurysms. We hope these results will improve the prediction of the disease and support the development of treatments to halt progression."
The study suggests further investigation into using existing osteoporosis medications as potential therapies for people at high risk for progressive aortic aneurysms.
