In a world where cutting-edge therapies often dominate the spotlight, it’s easy to overlook the potential of older drugs. Yet, history has shown that rediscovering forgotten therapies can be just as impactful as inventing new ones.

One such example is etidronate, a bisphosphonate that’s been around for decades but is now showing promise as a potential treatment for a rare and debilitating condition: Arterial Calcification due to Deficiency of CD73 (ACDC). This vascular disorder, caused by mutations in the NT5E gene, leads to painful calcifications in arteries, particularly in the lower limbs, significantly impairing patients’ mobility and quality of life.

Our recent article highlights an exciting development: etidronate might become the first standard treatment for ACDC. Early findings from a pilot study suggest that this older drug could slow disease progression and stabilize arterial calcifications, offering hope to those affected by this condition.

Why is etidronate worth revisiting?

Etidronate was one of the first bisphosphonates developed to treat bone-related disorders such as osteoporosis and Paget’s disease. However, its use declined as newer bisphosphonates like alendronate gained popularity for being more effective and better tolerated. But ACDC presents a unique challenge that sets it apart from traditional bone disorders.

The calcifications in ACDC arise from a genetic deficiency in CD73, an enzyme critical for regulating adenosine metabolism and preventing abnormal mineralization. This leads to calcium buildup in vascular tissues rather than bones. Etidronate’s ability to inhibit hydroxyapatite crystal formation directly targets this pathological calcification, making it a uniquely suitable option.

Unlike newer bisphosphonates, which primarily focus on suppressing bone resorption, etidronate’s distinct mechanism allows it to disrupt the calcification process at its core. This repositioning of an older drug highlights the need for innovation in the way we view and apply existing therapies.

The study: Encouraging yet preliminary

The pilot study investigating etidronate’s effects in ACDC involved a small group of patients with confirmed NT5E mutations. Over the treatment period, arterial calcifications were stabilized, with some participants also reporting reduced pain and improved mobility.

While these results are promising, they remain preliminary. Larger, long-term studies are necessary to validate these findings, optimize dosing regimens, and fully understand etidronate’s safety profile in this specific context. However, the study represents a crucial first step toward addressing a significant unmet need in rare disease management.

Implications beyond ACDC

ACDC isn’t the only condition that could benefit from etidronate. Similar genetic disorders characterized by pathological calcification—such as Generalized Arterial Calcification of Infancy (GACI) or Pseudoxanthoma Elasticum (PXE)—may also respond to this drug. The broader implications of etidronate’s mechanism of action could pave the way for tackling a range of genetic calcification disorders.

This case illustrates how drug repurposing can serve as a cost-effective and time-efficient solution, particularly for rare diseases. Developing a new drug from scratch is a lengthy and expensive process, often taking over a decade. By contrast, repurposing an existing drug with an established safety record allows researchers to fast-track the process, potentially bringing treatments to patients sooner.

Why this matters in the era of personalized medicine

Etidronate’s resurgence as a potential treatment for ACDC also underscores the importance of looking backward to move forward. In the age of personalized medicine, where therapies are increasingly tailored to genetic and molecular profiles, repurposing existing drugs provides an accessible and sustainable approach to innovation.

This strategy isn’t just about practicality—it’s about equity. Rare diseases like ACDC often receive limited attention and funding, leaving patients without meaningful treatment options. Exploring the untapped potential of older therapies ensures that advancements in medicine are inclusive, addressing the needs of underserved populations.

Moreover, revisiting older drugs aligns with broader efforts to promote sustainability in healthcare. By maximizing the utility of already-developed medications, we can reduce the environmental and economic burden of drug development while extending the benefits of medical innovation to more patients.

Challenges on the road ahead

Of course, challenges remain. Conducting larger clinical trials for rare diseases like ACDC is inherently difficult due to the small number of eligible patients. Securing funding and overcoming logistical barriers will require collaboration between researchers, pharmaceutical companies, and advocacy groups.

Etidronate’s pharmacokinetics and dosing must also be carefully optimized for this new application. Unlike its use in bone-related disorders, where dosing strategies are well-established, treating vascular calcification involves a different therapeutic target, necessitating tailored protocols to maximize benefits while minimizing risks.

Final thoughts

The story of etidronate is a reminder that innovation in medicine doesn’t always mean creating something new—it can also mean rediscovering the potential of what’s already available. In ACDC, a condition with no established treatment, etidronate offers a beacon of hope for patients and a testament to the power of repurposed therapies.

But this is about more than just one drug or one disease. It’s about rethinking how we approach the challenges of rare diseases, drug development, and personalized medicine. By revisiting older therapies with fresh eyes, we can uncover solutions that are both effective and equitable, advancing healthcare for all.

👉 What are your thoughts on the role of drug repurposing in rare diseases? Could etidronate’s success inspire a broader shift in how we approach treatment innovation? I’d love to hear your perspectives.

Check out the full article and join the conversation below.