Effects of Bone Marrow Derived Mesenchymal Stem Cells Versus Calcitonin on Mandibular Bone Defects in Osteoporotic Albino Rats

Background:Osteoporosis is a worldwide health problem with serious impact on the human population, particularly the post-menopausal women and elderly males as well. It causes reduced bone strength, delayed healing and increased liability to fractures. Different therapeutic options are routinely used for prevention and treatment of osteoporosis, calcitonin is considered one of the most currently used antiresorptive drugs. Recently, stem cell-based therapies have gained considerable clinical attention due to their potential and promise to treat a wide range of diseases including osteoporosis.
Objectives: to evaluate and compare the biological effects of bone marrow-derived mesenchymal stem cells versus calcitonin on healing of surgically induced mandibular bone defects performed on osteoporotic rats.
Materials and Methods: Fifty-seven healthy female albino rats weighing approximately 180-200 g were used in the study. Three of them were intramuscularly injected with saline once a week for five weeks then a unilateral surgical mandibular bone defect was created in the diastema region and they were considered negative control, while the other rats were intramuscularly injected with 7 mg/kg body weight dexamethasone sodium phosphate to induce osteoporosis-like condition then they were divided into three groups each included 18 rats. A unilateral surgical mandibular bone defects were created in rats of each group, one group did not receive any treatment and it was considered positive control group, the bone defects of another group were filled with absorbable hemostatic gelatin sponge seeded by 0.5×10⁶ bone marrow mesenchymal stem cells (BMSCs) while the bone defects of the last group were filled with absorbable hemostatic gelatin sponge loaded by 10 international unit of injectable synthetic salmon calcitonin. One rat was euthanized at the end of the 1^st, 2^nd and 4^th weeks postsurgically from group I while six rats from the other experimental groups were euthanized at the same timepoints. Then their mandibles were surgically removed and processed for histological analysis.
Results:
Histological results:
Rats of negative control group showed normal healing stages starting by formation of small amount of osteoid tissue at the defect peripheries surrounded by a mass of granulation tissue at the end of the 1^st week postsurgically. Two weeks after bone defect creation, the amount and thickness of the formed woven bone increased as detected by Haematoxylin and Eosin stain also the degree of bone maturation and calcification increased as revealed by Masson’s Trichrome. By the end of 4 weeks, a network of thicker well- organized bone trabeculae with narrower bone marrow cavities and increased maturity was formed.
The bone healing in the rats of the control positive group was obviously delayed when compared to negative control group, also, the formed bone was of poorer quality, quantity and maturation at the same timepoints.
The quantity, quality and maturation of the bone formed in the group treated by BMSCs seemed to surpass that of the other three groups at the same timepoints.
The histological results of the group treated by salmon calcitonin were better than that of the control groups at all timepoints but were comparable to that of stem cells’ group particularly at 1 week timepoint, but the maturation of bone was obviously better in salmon calcitonin group than the control groups at 2 and 4 weeks timepoints.
Conclusions:
Based on the previous results it was concluded that both BMSCs and salmon calcitonin are capable of treating mandibular bone defects in osteoporotic conditions but the bone regeneration in case of using BMSCs surpasses that when using calcitonin at same conditions. This was revealed in terms of better bone quantity, quality and maturation in favor of BMSCs