Acceleration of bone regeneration by activating Wnt/ß-catenin signalling pathway via lithium released from lithium chloride/calcium phosphate cement in osteoporosis.

By virtue of its excellent bioactivity and osteoconductivity, calcium phosphate cement (CPC) has been applied extensively in bone engineering. Doping a trace element into CPC can change physical characteristics and enhance osteogenesis. The trace element lithium has been demonstrated to stimulate the proliferation and differentiation of osteoblasts. We investigated the fracture-healing effect of osteoporotic defects with lithium-doped calcium phosphate cement (Li/CPC) and the underlying mechanism. Li/CPC bodies immersed in simulated body fluid converted gradually to hydroxyapatite. Li/CPC extracts stimulated the proliferation and differentiation of osteoblasts upon release of lithium ions (Li+) at 25.35 ± 0.12 to 50.74 ± 0.13 mg/l through activation of the Wnt/ß-catenin pathway in vitro. We also examined the effect of locally administered Li+ on defects in rat tibia between CPC and Li/CPC in vivo. Micro-computed tomography and histological staining showed that Li/CPC had better osteogenesis by increasing bone mass and promoting repair in defects compared with CPC (P < 0.05). Li/CPC also showed better osteoconductivity and osseointegration. These findings suggest that local release of Li+ from Li/CPC may accelerate bone regeneration from injury through activation of the Wnt/ß-catenin pathway in osteoporosis.

[Effect of a lithium-doped calcium phosphate cement in promoting tibial bone defect repair in rats].

OBJECTIVE: To evaluate the effects a lithium chloride-doped calcium phosphate cement (Li/CPC) on promoting tibial defect repair in rats. METHODS: Twenty 6-month-old female SD rats randomized into Li/CPC (n=10) and CPC control (n=10) groups. Surgery was performed to create bone defects at the bilateral tibia, which were filled with either of the cement. Five rats from each group were sacrificed at 1 and 2 months after the surgery for micro-CT examination and HE staining of the tibia. RESULTS: Micro-CT showed better repair of bone defects in Li/CPC group, which had a significantly higher new bone volume fraction (BV/TV) and a lower trabecular separation/spacing (Tb.Sp) than the control group (P<0.05). HE staining showed an earlier appearance of fiber and osteoid callus in Li/CPC group than CPC control group. The number and quality of bone healing was significantly higher in Li/CPC group than in CPC group. CONCLUSION: Li/CPC possessed better osteoinductivity and can significantly promote bone defect repair in rats.