Exploring New Therapeutic Uses for Cardiovascular Drugs in Bone Growth Disorders

Recent research has uncovered a promising new application for a well-established cardiovascular medication. Traditionally used to treat heart failure, thrombosis, and asthma, phosphodiesterase 3 (PDE3) inhibitors are now being studied for their potential to promote bone growth and address growth disorders.

Bone development occurs through the proliferation of chondrocytes, specialized cartilage cells located at the ends of long bones, and involves complex signaling pathways that regulate extracellular matrix (ECM) production. A key player in this process is the peptide hormone C-type natriuretic peptide (CNP), which activates a cascade involving cyclic guanosine monophosphate (cGMP), protein kinase G, and calcium influx via TRPM7 channels in chondrocytes. This signaling promotes ECM synthesis and subsequent bone growth.

Interestingly, the enzyme PDE3 degrades cGMP into GMP, thus attenuating the signaling pathway that encourages bone growth. PDE3 inhibitors, already approved for cardiovascular conditions, can increase intracellular cGMP levels by blocking this degradation, potentially enhancing CNP signaling in bone tissue.

A team of researchers led by Associate Professor Atsuhiko Ichimura of Ritsumeikan University and colleagues from Kyoto University investigated this potential. Their experiments, published in the British Journal of Pharmacology on June 2, 2025, involved both in vitro and in vivo studies. When mouse metatarsal bones were cultured with the PDE3 inhibitor cilostazol, there was a marked increase in bone length and expansion of chondrocyte zones.

Further, in in vivo studies, three-week-old mice treated with cilostazol for four weeks exhibited significant increases in body length, suggesting that PDE3 inhibitors can stimulate skeletal growth in young animals. Biochemical analyses confirmed that cGMP levels were approximately 1.7 times higher in treated bone tissues.

These findings highlight the potential for repurposing PDE3 inhibitors as therapeutic agents for growth disorders such as achondroplasia and idiopathic short stature. However, experts caution that these drugs should not be self-administered, as they carry risks like hypotension and blood clotting issues. Further clinical trials are necessary to evaluate safety and efficacy for these new indications.

Overall, this research opens up new avenues for skeletal growth regulation and provides hope for developing treatments for growth-related conditions, leveraging medications already known for their cardiovascular benefits.

Source: https://medicalxpress.com/news/2025-06-drug-potential-heart-growth-disorders.html