Glucocorticoid decreases circulating osteoprotegerin (OPG): possible mechanism for glucocorticoid induced osteoporosis.
BACKGROUND
Osteoporosis is a well known side-effect of long-term treatment with glucocorticoids. However, the precise mechanism of this disorder is unclear. Recently, osteoprotegerin (OPG) [osteoclastogenesis inhibitory factor (OCIF)] has been identified as a novel cytokine, which inhibits differentiation and activation of osteoclast. In the present study, in order to clarify the roles of OPG in the development of glucocorticoid-induced osteoporosis, we measured circulating OPG before and after glucocorticoid therapy.


METHODS
The study subjects were 12 patients (five males, seven females, 53.4 +/- 4.8 [SE] years) with various renal diseases that required glucocorticoid therapy. All patients received glucocorticoids for the first time. Treatment was initiated at an average dose of 32.5 +/- 3.0 mg per day. Serum OPG was measured using enzyme-linked immunosorbent assay (ELISA). Laboratory data, markers of bone metabolism and circulating OPG were compared before and after treatment for 4 weeks.


RESULTS
Serum OPG prior to glucocorticoid therapy was positively and independently correlated with serum creatinine. Serum OPG decreased significantly (P: < 0.0001) from 1.03 +/- 0.14 to 0.77 +/- 0.12 ng/ml after short-term administration of glucocorticoids. Furthermore, serum osteocalcin as a marker of bone formation was also reduced markedly (P: = 0.001). On the other hand, there were no remarkable changes in serum calcium, total alkaline phosphatases, creatinine and intact parathyroid hormone in response to glucocorticoid administration.


CONCLUSIONS
These findings indicate that short-term administration of glucocorticoids significantly suppresses serum OPG and osteocalcin. It might participate in the development of glucocorticoid-induced osteoporosis via an enhancement of bone resorption and suppression of bone formation.
Sasaki
N
N
Department of Nephrology, Jichi Medical School, Tochigi, Research Institute of Life Sciences, Snow Brand Milk Products Co., Ltd, Tochigi, Japan.
Kusano
E
E
Ando
Y
Y
Yano
K
K
Tsuda
E
E
Asano
Y
Y
D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects* / Q000627:therapeutic use*; D006023:Glycoproteins / Q000037:antagonists & inhibitors* / Q000097:blood*; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000037:antagonists & inhibitors / Q000097:blood; D010024:Osteoporosis / Q000097:blood* / Q000139:chemically induced*; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors* / Q000097:blood*; D018124:Receptors, Tumor Necrosis Factor
D005938:Glucocorticoids; D006023:Glycoproteins; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human; D015675:Osteocalcin