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.
Department of Nephrology, Jichi Medical School, Tochigi, Research Institute of Life Sciences, Snow Brand Milk Products Co., Ltd, Tochigi, Japan.
N
N
Sasaki
E
E
Kusano
Y
Y
Ando
K
K
Yano
E
E
Tsuda
Y
Y
Asano
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