OBJECTIVES: Previous studies have shown galanin (GAL) injections onto mouse calvaria increased bone thickness and osteoblast number. This study investigated the effects of the GAL receptor agonist galnon on bone loss using the ovariectomised (OVX) rat model. METHODS: OVX rats were treated with either vehicle or galnon for 6 weeks via mini-osmotic pumps. Plasma osteocalcin concentrations, osseous cell gene expression, morphological and biomechanical properties of the skeleton were compared between the two groups. RESULTS: Treatment with galnon increased RANKL:OPG gene ratio (p<0.001) plus expression of TNF-α (p<0.05) and cathepsin K (p<0.05). μCT analyses revealed galnon-treated OVX animals had reduced trabecular and cortical morphology compared to control animals. Biomechanically, galnon OVX animals required similar peak force to failure to that of control OVX animals although galnon treatment did enhance the mechanical properties of Young's modulus and ultimate tensile stress. CONCLUSIONS: Our research suggests that galnon, a GAL receptor agonist, may enhance osteoclastic bone resorption in OVX rats. Although galnon reduced bone volume, biomechanical testing revealed that bone of galnon-treated animals was mechanically superior per unit area. Taken together, galnon simultaneously improves the intrinsic quality of cortical bone whilst stimulating osteoclastic activity in the OVX rat model.