Modifications of biochemical markers of bone and collagen turnover during corticosteroid therapy.
Serum bone Gla protein (BGP), carboxyterminal cross-linked telopeptide of type I collagen (ICTP) and aminoterminal propeptide of type III procollagen (PIIINP) levels were determined in 8 patients with autoimmune disorders (2 with systemic lupus erythematosus, 3 with rheumatoid arthritis, 2 with Sjögren's syndrome and 1 with mixed connective tissue disease) before and after 1, 2 and 4 months of treatment with oral prednisone (at a dosage of 1 mg/kg bw/day, p.o. during the first month, then reduced to 0.1-0.2 mg/kg bw/day). Before treatment mean serum BGP (mean +/- SE: 5.3 +/- 0.4 ng/ml) and ICTP (2.8 +/- 0.2 ng/ml) levels were similar to those recorded in an age and sex matched control group (n = 40: 5.4 +/- 0.1 ng/ml and 4.1 +/- 0.3 ng/ml, respectively). On the other hand, serum PIIINP levels (2.2 +/- 0.3 ng/ml) were significantly (p < 0.008) lower than those found in controls (3.3 +/- 0.2 ng/ml). During glucocorticoid therapy, serum BGP levels significantly decreased after 1 month (2.9 +/- 0.4 ng/ml; P < 0.001), but returned to baseline values after 2 and 4 months of treatment (4.7 +/- 0.4 ng/ml and 5.3 +/- 0.3 ng/ml, respectively). On the contrary, no significant changes were observed in serum ICTP levels during treatment (1st month: 2.7 +/- 0.4 ng/ml; 2nd month: 3.0 +/- 0.4 ng/ml; 4th month: 2.4 +/- 0.3 ng/ml). Serum PIIINP mean concentration significantly decreased after 1 (1.6 +/- 0.3 ng/ml; P < 0.004) and 2 months of glucocorticoid administration (1.5 +/- 0.2 ng/ml; P < 0.01); after 4 months, serum PIIINP levels were again reduced as before therapy (1.8 +/- 0.2 ng/ml). In conclusion, our study shows the presence of normal bone turnover indexes and of altered collagen synthesis in patients with autoimmune disorders. The use of high doses of oral steroids is associated with a prompt decrease of bone formation and collagen synthesis, without any significant changes in bone resorption; however, the negative effects on bone formation and collagen synthesis seem to revert after lowering corticosteroid dosage. Serial determinations of the markers of bone and collagen turnover are able to give useful and reliable information on the peripheral effects of steroids excess.
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Laboratorio Sperimentale di Ricerche Endocrinologiche, Centro Auxologico Italiano, IRCCS, Milano, Italy.
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Ambrosi
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D000328:Adult; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy; D001327:Autoimmune Diseases / Q000097:blood / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D001842:Bone and Bones / Q000378:metabolism*; D003094:Collagen / Q000097:blood*; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D008947:Mixed Connective Tissue Disease / Q000097:blood / Q000188:drug therapy; D015675:Osteocalcin / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011241:Prednisone / Q000627:therapeutic use*; D011347:Procollagen / Q000097:blood*; D012859:Sjogren's Syndrome / Q000097:blood / Q000188:drug therapy
D015415:Biomarkers; D010446:Peptide Fragments; D011347:Procollagen; C041876:procollagen Type III-N-terminal peptide; D015675:Osteocalcin; D003094:Collagen; D011241:Prednisone