Long-term comparative study of Substance-P with methylprednisolone on the development of osteoporosis

Steroids are treated for most inflammatory diseases but cause serious side effects such as diabetes and osteoporosis after their long-term usage. Recently, we identified novel roles of Substance-P (SP) in the suppression of the injury-mediated inflammation and also in stem cell mobilization. In this study, for clinical application of SP as an anti-inflammatory agent, its safety in long-term usage was evaluated with regard to diabetes and osteoporosis. Dexamethasone (DEX) and methylprednisolone (MP) were used as comparative drugs. While DEX-injection for 24 weeks developed severe weight loss, unstable blood glucose, and bone loss, SP-injection did not affect blood glucose and bone mass. MP-injection for 24 weeks also influenced blood glucose and body weight much milder than DEX-injection. After 66 weeks, MP-injection caused unstable blood glucose, alleviation in the age-related increase of body weight, and bone weakness, which was featured by reduction in collagen deposition and trabecular bone volume based on histological and micro CT analysis. However, SP-injection for 66 weeks rather increased collagen deposition, bone volume, and bone density. Therefore, this comparative study suggests that SP, even after long-term usage of effective dose, may not cause side effects such as osteoporosis in comparison to that of DEX and MP and can be developed as an anti-inflammatory agent and/or stem cell mobilizer for long-term treatment.