Exploring etidronate treatment for arterial calcification: A pilot study on ACDC

The researchers found that etidronate treatment slowed the progression of further vascular calcification in the lower extremities as measured by computed tomography (CT), but the treatment had no effect on reversing vascular and/or periarticular joint calcifications.

Arterial calcification due to CD73 deficiency is a rare genetic disease resulting in calcium deposits in arteries and small joints causing resting pain, claudication, deformities, and severe joint pain. Currently, no standard treatments exist for ACDC. Previous studies have identified etidronate as a potential targeted ACDC treatment, using in vitro and in vivo disease models with patient-derived cells.

Etidronate, a bisphosphonate with established efficacy in inhibiting bone resorption and preventing osteoporosis, has garnered interest for its potential role in mitigating pathological calcification in ACDC. By binding to hydroxyapatite crystals and interfering with their formation and growth, etidronate exhibits anti-calcification properties that could translate into therapeutic benefits for individuals with ACDC.

In the study, Elisa A Ferrante, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA, and colleagues tested the effectiveness and safety of etidronate in attenuating the progression of lower-extremity arterial calcification and vascular blood flow based on the ankle-brachial index (ABI) and computed tomography (CT) calcium score.

For this purpose, the researchers conducted an open-label, nonrandomized, single-arm pilot study for etidronate treatment enrolling adult patients with a confirmed genetic diagnosis of ACDC. They took daily etidronate for 14 days every 3 months and were examined at the NIH Clinical Center bi-annually for 3 years.

They received a baseline evaluation and yearly follow-up after treatment. Study visits included exercise tolerance tests with ABIs, imaging studies, clinical blood and urine testing, and full dental exams.

The study found that etidronate treatment appeared to have slowed the progression of further vascular calcification in lower extremities as measured by CT but has no impact in reversing vascular and/or periarticular joint calcifications in the small ACDC cohort.

"Despite the small sample size, these findings potentially suggest that etidronate could be considered for patients with progressive vascular calcification due to ACDC, particularly given the total lack of any other treatment options for this disease," the authors wrote.

"In addition, the knowledge gained for the pathology, natural history, and clinical presentation of ACDC has been invaluable and will inform the development of novel therapies and larger clinical trials for this and other calcifying vascular diseases."

Reference:

Ferrante, E. A., Cudrici, C. D., Rashidi, M., Fu, P., Huffstutler, R., Carney, K., Chen, M. Y., St Hilaire, C., Smith, K., Bagheri, H., Katz, J. D., Ferreira, C. R., Gahl, W. A., Boehm, M., & Brofferio, A. (2024). A pilot study to evaluate the safety and effectiveness of etidronate treatment for arterial calcification due to deficiency of CD73 (ACDC). Vascular Medicine. https://doi.org/10.1177/1358863X241235669