What Is Neridronate?
Neridronate, also known as neridronic acid, is a nitrogen-containing bisphosphonate medication developed in Italy [1.6.3]. Bisphosphonates are a class of drugs that prevent the loss of bone density, used to treat osteoporosis and similar diseases. Neridronate is notable for its use in treating Complex Regional Pain Syndrome (CRPS), Osteogenesis Imperfecta (OI), and Paget's disease of the bone [1.5.3, 1.6.4]. It can be administered both intravenously (IV) and intramuscularly (IM), offering flexibility that distinguishes it from some other bisphosphonates [1.7.2]. In Italy, the national regulatory agency, AIFA, has approved neridronate for these conditions, making it a standard part of care there [1.2.3, 1.3.5].
Mechanism of Action
Like other potent, nitrogen-containing bisphosphonates, neridronate works by inhibiting osteoclasts, the cells responsible for bone breakdown [1.6.3]. It binds strongly to hydroxyapatite, a major component of bone, and interferes with key cellular processes within osteoclasts, leading to their inactivation [1.6.3, 1.6.5]. This action reduces bone resorption and turnover. For conditions like CRPS, researchers believe it helps by stopping the pathological bone breakdown and fluid accumulation in the bone marrow associated with the syndrome [1.2.1]. It may also have anti-inflammatory effects that contribute to pain relief [1.4.6]. Studies suggest it may also have a potential anabolic effect on osteoblasts, the cells that form new bone [1.6.1, 1.6.4].
The FDA and Availability in the US
As of late 2025, neridronate is not approved by the U.S. Food and Drug Administration (FDA) and is not commercially available in the United States [1.2.1, 1.3.2]. It remains an investigational drug in the US [1.2.2].
Despite this, neridronate has garnered significant interest. The FDA has granted it several special statuses based on promising early data for the treatment of CRPS:
- Orphan Drug Designation (March 2013): This status is for drugs intended to treat rare diseases or conditions [1.8.1, 1.8.2].
- Fast Track Designation (August 2015): This is designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need [1.8.2].
- Breakthrough Therapy Designation (December 2016): This is granted to drugs that show substantial improvement over available therapy on a clinically significant endpoint [1.2.2, 1.8.2].
However, these designations do not guarantee approval. Phase III clinical trials in the US, sponsored by Grünenthal, have been conducted to evaluate the safety and efficacy of neridronate for CRPS [1.2.5]. Some trials have been halted or produced results that did not show a significant difference between the drug and a placebo, creating setbacks on its path to approval [1.4.7]. Patients in the U.S. seeking this treatment must either enroll in a clinical trial (when available) or travel to countries like Italy where it is approved [1.3.4, 1.2.7]. Some U.S. clinics may offer legally permissible "off-label" use of equivalent bisphosphonate medications, but not neridronate itself [1.2.4, 1.3.1].
Neridronate for Specific Conditions
- Complex Regional Pain Syndrome (CRPS): Neridronate is the only treatment officially approved by a national regulatory agency (in Italy) specifically for CRPS [1.2.3]. Studies have shown that it can provide a robust and clinically significant improvement in pain and function, particularly when used in the early stages of the disease [1.4.3]. The standard treatment protocol in Italy involves four IV infusions over a 10-day period [1.6.2].
- Osteogenesis Imperfecta (OI): Neridronate is also licensed for use in OI in Italy [1.5.1]. Studies in both children and adults have shown that it can significantly increase bone mineral density (BMD) and reduce fracture risk [1.5.2, 1.5.4]. Its less frequent administration schedule compared to other bisphosphonates like pamidronate is considered a benefit for quality of life [1.7.3].
Comparison with Other Bisphosphonates
Neridronate belongs to the same class as other well-known bisphosphonates like alendronate (Fosamax), pamidronate (Aredia), and zoledronic acid (Reclast, Zometa).
| Feature | Neridronate | Zoledronic Acid (Reclast) | Alendronate (Fosamax) |
|---|---|---|---|
| Administration | IV, IM [1.7.2] | IV (yearly for osteoporosis) [1.7.6] | Oral (daily or weekly) [1.7.5] |
| US FDA Approval | No (Investigational) [1.2.1] | Yes (for osteoporosis, Paget's, etc.) [1.7.6] | Yes (for osteoporosis, Paget's) [1.7.5] |
| GI Side Effects | Minimal (parenteral use) [1.7.2] | Minimal (IV use) [1.7.6] | Common; strict dosing rules [1.7.5] |
| Approved for CRPS | Yes (in Italy) [1.2.3] | No (used off-label) | No (used off-label) |
| Potency | Potent nitrogen-containing BP [1.6.3] | Most potent BP available [1.7.6] | Potent nitrogen-containing BP |
Studies comparing neridronate to zoledronate for Paget's disease found similar efficacy [1.7.1]. A key advantage of parenteral (IV/IM) bisphosphonates like neridronate and zoledronate over oral ones like alendronate is the avoidance of gastrointestinal side effects and issues with poor absorption [1.7.5].
Potential Side Effects
Though generally well-tolerated, neridronate can have side effects similar to other IV bisphosphonates. The most common is an acute-phase reaction, which can include flu-like symptoms such as fever and muscle or joint pain shortly after infusion [1.6.6]. More serious, but rare, side effects associated with the bisphosphonate class include osteonecrosis of the jaw (ONJ) and atypical femur fractures [1.6.6].
Conclusion
In conclusion, while neridronate is a promising medication used successfully in Italy for debilitating conditions like CRPS and OI, it is not available in the US as a commercially approved treatment [1.3.1, 1.3.2]. Despite receiving multiple expedited designations from the FDA, clinical trials have not yet led to its approval. The future of neridronate in the United States hinges on the results of ongoing and future clinical trials demonstrating its safety and efficacy to the satisfaction of the FDA. Until then, American patients face the difficult choice of pursuing limited clinical trial access, exploring off-label use of similar drugs, or traveling abroad for care.
For more information on clinical trials, one authoritative source is ClinicalTrials.gov.
