Less Vertebral Bone Mass after Treatment with Macitentan in Mice: A Pilot Study

Area of Science:

• Endocrinology
• Bone Biology
• Pharmacology

Background:

• The skeleton and vasculature are interconnected systems.
• Endothelin-1 (ET-1) influences both blood vessel constriction and bone metabolism.
• Macitentan, a dual endothelin-1 receptor antagonist, treats pulmonary arterial hypertension, but its skeletal effects are understudied.

Purpose of the Study:

• To investigate the impact of Macitentan treatment on vertebral bone mass in a mouse model.
• To understand the potential secondary effects of Macitentan on skeletal health.

Main Methods:

• Male balb/c mice were divided into control (vehicle) and treatment (Macitentan) groups.
• Administration was via intraperitoneal injection for 4 months.
• Vertebral bone mass was assessed using microcomputed tomography and histology; plasma ET-1 levels were measured via ELISA.

Main Results:

• Macitentan-treated mice exhibited elevated plasma endothelin-1 levels.
• Vertebral bone mass was significantly reduced in the treatment group compared to controls.
• Histological analysis revealed fewer osteoblasts and more osteoclasts in the vertebral trabecular bone of treated mice.

Conclusions:

• Macitentan treatment is associated with decreased vertebral bone mass in mice.
• These findings highlight potential adverse skeletal effects of dual endothelin-1 receptor antagonists.
• Further research is needed to explore the underlying molecular mechanisms involving osteoblasts and osteoclasts.