Propranolol Attenuates Risperidone-Induced Trabecular Bone Loss in Female Mice

Area of Science:

• Bone Biology
• Pharmacology
• Endocrinology

Background:

• Atypical antipsychotics (AA) are associated with metabolic side effects, including increased fracture risk and bone loss, particularly with risperidone (RIS).
• The mechanisms linking AA treatment to bone loss are not fully understood.
• The sympathetic nervous system (SNS) is implicated in regulating bone remodeling.

Purpose of the Study:

• To investigate the role of the sympathetic nervous system (SNS) in mediating bone loss induced by atypical antipsychotics (AA), specifically risperidone (RIS).
• To determine if blocking SNS activity can prevent AA-induced bone loss.

Main Methods:

• Administered risperidone (RIS) to mice and assessed bone parameters (trabecular bone volume, osteoclast erosion, osteoblast formation).
• Measured markers of SNS activity and thermogenesis (Pgc1a, Ucp1) and osteoclast recruitment factor (Rankl) after RIS administration.
• Co-administered RIS with propranolol (a beta-blocker) or used beta2-adrenergic receptor null (Adrb2(-/-)) mice to assess the role of SNS signaling.

Main Results:

• RIS treatment in mice significantly reduced bone volume by increasing osteoclast activity and decreasing osteoblast activity.
• RIS administration transiently increased SNS activity markers and Rankl expression.
• Co-administration with propranolol or the use of Adrb2(-/-) mice completely prevented RIS-induced bone loss, erosion, and formation changes.

Conclusions:

• Atypical antipsychotic-induced bone loss is, at least partially, regulated by the sympathetic nervous system.
• Blocking beta-adrenergic signaling prevents risperidone-induced bone loss in mice.
• Clinical studies are warranted to explore beta-blocker use for preventing bone loss in patients treated with atypical antipsychotics.