Low dose lithium supplementation activates Wnt/β-catenin signalling and increases bone OPG/RANKL ratio in mice.

Lithium, a well-known inhibitor of glycogen synthase kinase-3β (GSK3β), can improve bone formation by activating the Wnt/β-catenin signalling pathway. However, most studies have used higher doses of lithium, which potentially have adverse effects. Herein, we report that low dose lithium supplementation (10 mg/kg/d for 6 weeks) in mice results in a serum lithium concentration of 0.02 mM significantly inhibiting GSK3β while activating Wnt/β-catenin in bone. In turn, we observed a significant increase in the expression of osteoprotegerin (OPG), with unaltered expression of nuclear-factor kβ ligand (RANKL), ultimately leading to a significant increase in the OPG/RANKL ratio. Altogether, our findings provide initial evidence that low dose lithium supplementation can promote the signalling pathways associated with bone formation.