Investigating the Preventive Effects of 99Tc-Methylenediphosphonate on a Glucocorticoid-Induced Osteoporosis Rabbit Model

Abstract

Background and objective: Osteoporosis is a worldwide healthcare challenge. Conventional medications for osteoporosis prevention are not clinically effective or associated with gastrointestinal tract adverse effects. The present study aimed to comparatively investigate the effects of technetium-99 conjugated with methylene diphosphonate (⁹⁹Tc-MDP) and calcium carbonate and alendronate on the prevention and treatment of osteoporosis in glucocorticoid-induced osteoporosis rabbit model through evaluating bone alkaline phosphatase (B-ALP), TRAP-5b levels and histopathological parameters.

Methods: Forty healthy female New Zealand rabbits were randomly divided into five groups (each n=8), including control group (Control Group), osteoporosis model group (GIO Group), osteoporosis model + ⁹⁹Tc-MDP group (⁹⁹Tc-MDP Group), osteoporosis model + alendronate group (Alendronate Group), and osteoporosis model + calcium carbonate group (calcium carbonate Group). Animals in each group were treated with corresponding interventions for 14 weeks. The blood samples were collected at the first and 14th week, and B-ALP and TRAP-5b levels were detected by enzyme- linked immunosorbent assay (ELISA). The rabbits were anesthetized at the 14th week, and pathological cytological observation was performed on both femurs.

Results: The age and weights of rabbits in different groups had no statistically significant differences (P>0.05). B-ALP levels in serum of all groups except for the Control Group decreased after treatment, but the differences were not statistically significant (P>0.05). TRAP-5b levels in serum of all groups increased after treatment. Specifically, differences in the GIO Group and calcium carbonate group were statistically significant (P<0.05), while differences in ⁹⁹Tc-MDP Group and alendronate Group were not statistically significant (P<0.05). Pathological sections revealed that the control group presented normal bone tissue morphology. The bone tissue morphology of the ⁹⁹Tc- MDP group and alendronate group was similar to control group and GIO group. Moreover, the calcium carbonate group and GIO group exhibited similar bone tissue morphology.

Conclusion: ⁹⁹Tc-MDP has a preventive effect on the glucocorticoid-induced osteoporotic rabbit model. This osteoporosis preventive effect might be attributed to the capacities of ⁹⁹Tc-MDP in promoting the osteoblasts generation and inhibiting the generation and reducing the activity of osteoclasts.

Keywords: 99Tc-methylenediphosphonate (99Tc-MDP); Bone tissue; Glucocorticoid; Osteoblast; Osteoclasts; Osteoporosis; Osteoporosis..