Treatment with α-lipoic acid enhances the bone healing after femoral fracture model of rats.

ABSTRACT

This study investigated the fracture-healing effects of α-lipoic acid (α-LA), which was applied orally once daily in preventive treatment mode during 1 month after fracture induction. Rats were randomly divided into sham-operated group (group 1), femoral fracture control (group 2), femoral fracture + 25 mg/kg α-LA (group 3), and femoral fracture + 50 mg/kg α-LA (group 4). Rats in the experimental groups were orally administered 25 or 50 mg/kg α-LA once daily for 30 days starting from postoperative day 1. Thirty days postoperatively, the rats underwent X-ray imaging and were then euthanized for blood and tissue collection. Histopathological, biochemical, molecular, computed tomography (CT), and mechanical strength tests were performed on samples. The serum levels of osteocalcin (OC), osteopontin (OP), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) did not differ significantly between groups 2 and 3. Serum OC, OP, TNF-α, and IL-6 levels in group 4 were significantly lower than those in group 3. From X-ray images, staging for fracture healing was scored as <2 in group 2, >2 in group 3, and >3 in group 4. In group 2, the average score of less than 2 suggests insufficient fracture healing; those of both the α-LA groups were >2, indicating progression of healing. Transforming growth factor beta (TGF-ß) messenger RNA (mRNA) levels were significantly higher in the sham group than in the femoral fracture control. Both doses of α-LA increased TGF-ß mRNA expression compared to the fracture group. CT results and biomechanical testing at 4 week after fracture demonstrated that α-LA has fastened bone healing, which was confirmed by stereological analyses in which 50 mg/kg α-LA increased the number of osteoclasts. Our findings indicate that α-LA supplementation promotes healing of femoral fractures in rats.