title: Variance of spinal osteoporosis induced by dexamethasone and methylprednisolone and its associated mechanism.
abstract: BACKGROUND
  Glucocorticoid (GC) administration is the most common cause of secondary osteoporosis. Previous studies investigated GCs dose and frequency correlated positively with the side effects of glucocorticoid on bone health, however the impaired effect of various types of GCs on bone has not yet been reported.
  
  
  OBJECTIVE
  The aim is to compare the effect of long-acting (dexamethasone) and relatively short-acting glucocorticoid (methylprednisolone) on rat lumbar spine and try to explore the associated mechanism.
  
  
  METHODS
  Sprague Dawley rats (N=48) were randomly divided into four groups: baseline group (BL), control group (CON), methylprednisolone group (MP) and dexamethasone group (DEXA). BL rats were euthanized to remain as baseline (M0) at the beginning of experiment. CON group were injected daily with vehicle, while the other groups were given a daily subcutaneous injection of 1mg/kg methylprednisolone and were given a subcutaneous injection of 0.6mg/kg dexamethasone per 3days, respectively. CON, MP and DEXA groups were monitored at 4th week (M1), 8th week (M2) and 12th week (M3) after intervention. Dual-energy X-ray, micro-computed tomography, compressive test, enzyme-linked immunosorbent assay have been used for bone mineral density, microarchitecture, biomechanical property of vertebrae and levels of estrogen, PINP and β-CTX, respectively. mRNA expression analysis of Biglycan, Col1a1, MMP9, Cathepsin K, Runx2, OPG, LRP5, Sclerostin were performed.
  
  
  RESULTS
  We found that the bone mineral density (BMD) was significantly lower in DEXA rats at M3 compared with MP rats. The relative surface and trabecular number were significantly lower in DEXA group than that in MP group at M2, while trabecular separation was significantly higher in DEXA group than that in MP group at the same point. The compressive strength was significantly lower in L4 of DEXA than that in MP rats at M2 and M3. The levels of both PINP and estradiol in DEXA group were lower than MP group at M3, even though without statistical significance. The expression of bone formation marker Runx2 was significantly down-regulated at M3 in DEXA group compared with MP, CON and BL groups, while the expression of Col1a1 was significantly up-regulated and biglycan, LRP-5, OPG were significantly down-regulated in GCs intervention groups compared with CON and BL groups. There were no statistical differences in MMP9, Cathepsin K, Sclerostin among CON, MP and DEXA groups.
  
  
  CONCLUSIONS
  These results indicate that dexamethasone, the long-acting glucocorticoid, generates more serious osteoporosis of rat lumbar spine than methylprednisolone, which is relatively short-acting glucocorticoid. The discrepancy between the two GCs inducing osteoporosis may be mainly caused by a decrease in bone formation. RUNX2 and Col1a1 may be the two of critical genes inducing the discrepant impairment.
authors.affiliation: The First School of Clinic Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, China. Electronic address: 513469239@qq.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Ren
authors.affiliation: Department of Spinal Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Laboratory Affiliated to National Key Discipline of Orthopaedic and Traumatology of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, China. Electronic address: 513469239@qq.com.
authors.forename: De
authors.initials: D
authors.lastname: Liang
authors.affiliation: Department of Spinal Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Laboratory Affiliated to National Key Discipline of Orthopaedic and Traumatology of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, China. Electronic address: spinedrjxb@sina.com.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Jiang
authors.affiliation: The First School of Clinic Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Tang
authors.affiliation: The First School of Clinic Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
authors.forename: Jianchao
authors.initials: J
authors.lastname: Cui
authors.affiliation: Laboratory Affiliated to National Key Discipline of Orthopaedic and Traumatology of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Postdoctoral Programme, General Hospital of Guangzhou Military Command of Chinese PLA, Guangzhou 510010, China.
authors.forename: Qiushi
authors.initials: Q
authors.lastname: Wei
authors.affiliation: Department of Spinal Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
authors.forename: Shuncong
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Spinal Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
authors.forename: Zhensong
authors.initials: Z
authors.lastname: Yao
authors.affiliation: The First School of Clinic Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
authors.forename: Gengyang
authors.initials: G
authors.lastname: Shen
authors.affiliation: The First School of Clinic Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
authors.forename: Shunxin
authors.initials: S
authors.lastname: Lin
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D003907:Dexamethasone / Q000009:adverse effects* / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D008775:Methylprednisolone / Q000009:adverse effects* / Q000494:pharmacology; D010024:Osteoporosis / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013131:Spine / Q000378:metabolism* / Q000473:pathology
chemical_list: D003907:Dexamethasone; D008775:Methylprednisolone
keywords: Dexamethasone; Glucocorticoid-induced osteoporosis; Mechanism; Methylprednisolone; Variance