Abstract: BACKGROUND: Deferoxamine mesylate is a potential anti-osteoporosis drug with iron chelation, vascular regeneration, and antioxidant effects. Recent studies have shown that the application of deferoxamine mesylate can be extended to the field of tissue regeneration engineering.
OBJECTIVE: To investigate whether deferoxamine mesylate can promote the repair effect of iron overload osteoporotic rats after bone grafting for mandibular bone defects by simulating the state of iron accumulation in patients with postmenopausal osteoporosis with high iron intervention in osteoporotic rats.
METHODS: An iron accumulation ovariectomized osteoporosis model was firstly constructed. The model group underwent bilateral ovariectomy, and the intraperitoneal injection of ferric ammonium citrate (90 mg/kg, twice a week, for 11 weeks) was started in the 2nd week, while the sham-operated group had some fat around the ovaries removed and was given an equal amount of saline for 11 weeks. After the successful modeling, the experimental rats were divided into sham-operated group (n=6), high iron ovariectomtized group (n=6) and high iron ovariectomized deferoxamine mesylate treatment group (deferoxamine mesylate group, n=6). Bone defects of 5 mm in diameter were established in the rat’s bilateral mandibles and implanted with Bio-Oss bone powder. Intraperitoneal injection of deferoxamine mesylate (100 mg/kg, 3 times a week) was started on postoperative day 4 in the deferoxamine mesylate group, and equal volume of saline was given in the sham-operated and high iron ovariectomized groups. The bone samples of the mandible, liver and blood were taken at 2 and 12 weeks after bone grafting for Prussian blue staining of the jaw and liver and ELISA detection of serum ferritin to detect iron levels in various body tissues; hematoxylin-eosin staining and Masson staining were performed to observe inflammatory cell infiltration and early osteogenesis in the bone defect area; tartrate resistant acid phosphatase staining was performed to observe osteoclast differentiation; ELISA was performed to detect serum calcitonin and type I collagen C-terminal peptide levels; and Micro-CT and hematoxylin-eosin staining were performed to observe osteogenesis in the middle and late stages.
RESULTS AND CONCLUSION: The number of tibial trabeculae was reduced and the trabeculae were sparsely arranged in the high iron ovariectomized group. Iron levels in the liver, jaw bone and serum were significantly higher in the high iron ovariectomized group than the sham-operated group at 2 weeks after bone grafting, while the iron levels were significantly decreased after deferoxamine mesylate intervention (P < 0.05). In the early stage of bone defect repair, more inflammatory cell infiltration, less new bone matrix and less type I collagen fiber production were observed in the high iron ovariectomized group than in the sham-operated group (P < 0.05); after deferoxamine mesylate treatment, inflammatory cell infiltration was reduced, a small amount of new bone matrix was produced and collagen fibers increased significantly (P < 0.05). In the middle and late stages of bone defect repair, Micro-CT results showed a reduction in new bone production in the high iron ovariectomized group compared with the sham-operated group and increased new bone matrix after deferoxamine mesylate treatment (P < 0.05). Compared with the sham-operated group, the osteoclast number, serum calcitonin level, and serum type I collagen C-terminal peptide level were increased in the high-iron ovariectomized group, while the osteoclast number was decreased and bone metabolic indexes were improved after treatment with deferoxamine mesylate. To conclude, in ovariectomized rats with high iron intervention, elevated iron levels can be seen in multiple tissues, accompanied by reduced new bone production in the mandibular bone defect area. Deferoxamine mesylate can improve bone metabolism and inhibit osteoclast activity by removing iron deposits in tissues, improve bone formation in iron-accumulated osteoporotic rats, and promote bone healing in the mandibular bone defect area.

Key words: deferoxamine mesylate, osteoporosis, iron, bone defect, osteogenesis