Preclinical evaluation of osteogenic effects of 99Tc-MDP in osteoporosis models

[Background]: Bone fracture is an important factor affecting the life quality and mortality of elderly individuals, and its pathogenesis involves the imbalance of bone metabolism maintained by osteoblasts (OB) and osteoclasts (OC). 99Tc-MDP is a drug for the targeted treatment of osteoporosis. While it can directly inhibit OC activity, there have been no in vivo data on its ability to induce OB activity. [Purpose]:This study aim to evaluate the effect of 99Tc-MDP on osteogenesis in the treatment of osteoporosis. [Methods]: In this study, a rat model of osteoporosis after ovariectomy were constructed, and the dynamic changes of osteoblast indexes after 99Tc-MDP treatment were detected at the cellular, metabolic, and genetic levels to evaluate the effect of 99Tc-MDP on osteogenesis in the treatment of osteoporosis. The rat model of osteoporosis can reflect the early process of osteoporosis formation, including calcium loss and bone mineral density decrease. [Results]: 99Tc-MDP effectively inhibited the osteoporosis process and reversed bone mineral density loss by inducing OB activity, achieving the suppression of bone decline at 4 weeks and returning to the preoperative level at 8 weeks. The OB activity induced by 99Tc-MDP was altered to similar levels in OB cells of normal rats, but there was no significant change in the expression of major bone-related genes. The multifactor analysis suggested that IL-6 could be the key factor and monitoring index. [Conclusions]: 99Tc-MDP can stimulate OB activity as a powerful supplement to inhibiting OC activity, which is beneficial to the maintenance of OB/OC homeostasis.