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.
College of Medicine/East-West Medical Research Institute, Kyung Hee University.
Hyun Sook
HS
Hong
Jihyun
J
Um
Zang Hee
ZH
Lee
Youngsook
Y
Son
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D007267:Injections; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000009:adverse effects*; D010024:Osteoporosis / Q000139:chemically induced* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology; D013373:Substance P / Q000008:administration & dosage / Q000009:adverse effects*; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D001786:Blood Glucose; D013373:Substance P; D003907:Dexamethasone; D003094:Collagen; D008775:Methylprednisolone