Short-term glucocorticoid treatment causes spinal osteoporosis in ovariectomized rats

Abstract

Short-term glucocorticoid treatment of ovariectomized rats indicates according to DEXA standards a severe osteoporotic bone status in vertebral bone. Nonetheless, dysfunctional bone anabolism and enhanced bone catabolism are observed. Alterations of bone extracellular matrix proteins that correlate to inferior mechanical stability and affected microstructure were noticed and suggest further investigation. Treatment with dexamethasone was also seen to affect insulin and osteopontin levels and thus osteoblast function and maturation. This described animal model presents a recapitulation of clinically obtained data from early phase glucocorticoid-induced osteoporosis observed in patients.

Variance of spinal osteoporosis induced by dexamethasone and methylprednisolone and its associated mechanism

“…Being identical to the results of previous reports [16], which demonstrated that GCs induced high turnover osteoporosis, our test about serum levels of bone turnover markers indicates GCs increase activities of bone formation and resorption but decrease bone mass, which suggest bone metabolic imbalance resulted from relatively reduced bone formation or elevated bone resorption. In this study, serum levels of PINP and β-CTX in DEXA group are lower than MP group, indicating that more notable bone mass loss induced by dexamethasone might be related with comparatively lower activity of bone formation.…”

“…These results seem to conflict with some of previous studies which reported that MMP9, Sclerostin, Cathepsink were up-regulated [16,32,50]. However, in fact, this confliction may attribute to multiple factors such as different duration of GCs intervention and varied site of bone sample.…”

“…However, estrogen deficiency may not be the main cause of the discrepancy between the osteoporosis induced by different GCs according to the data without significant difference in the two GCs groups. Since deficiency of Estrogen mainly elevated the activities of osteoclasts to induce bone mass loss [16,39], more severe osteoporosis induced by DEXA may be correlated with the lower activity of bone formation in the current experiment.…”

“…Furthermore, low osteoclast markers expression at M3 may be the result from decreased acid secretionor inefficient bone resorption [51,53]. GIOP occurs in two phases: an rapid initial phase of maximal bone turnover which BMD reduced dramatically due to excessive bone resorption, and a relatively slow latter phase associated with high turnover which BMD declined slowly due to impaired bone formation [16,26,32,51,[53][54][55]. So our results may be stayed in latter phase.…”

“…Since the inhibition of bone formation and promotion of bone resorption induced by GCs mainly reduced trabecularbone mass [3,12,13], vertebral bodies, which are composed of 95% trabecular bone and 5 % cortical bone [14][15][16], are more susceptible to GIOP than the long bones in the extremities [16]. To improve the sensitivity in this comparative study, we designated the bone quality and quantity of rat lumbar spine as the main study objects.…”