Effect of Glucocorticoid-, Parathyroid- and Thyroid Hormones Excess on Human Iliac Crest Bone Matrix Insulin-like Growth Factor (IGF)-I in Patients with Osteoporosis

Abstract

Insulin-like growth factor-I (IGF-I) is a well documented bone-active growth factor. Clinical studies reported that circulating hormones may affect serum IGF-I levels, with potential consequences on bone remodeling. However, no data on bone matrix concentrations of IGF-I in subjects with endocrine dysfunction is available in humans. Bone mineral density and cancellous bone matrix IGF-I levels were assessed in iliac crest biopsies from 38 patients with low bone mass related to glucocorticoid- (n=10), parathyroid- (n=14) or thyroid (n=14) hormones excess. Results were compared to those of sex- and age-matched patients with primary osteoporosis. Bone matrix extraction was performed based on a guanidine-chlorhidric acid/ethylendiamine-tetraacetic acid method. Long-term glucocorticoid therapy (≥24 months) led to significantly lower cancellous bone matrix IGF-I levels in comparison to age-matched controls (p=0.03). Although higher trabecular bone IGF-I levels were seen in hyperparathyroid subjects, the difference was not significant in comparison to controls (p=0.24). Likewise, no difference was noticed in cancellous bone matrix IGF-I concentrations between subjects with low bone mass and sub-clinical or overt thyrotoxicosis and euthyroid controls. Neither parathyroid hormone (PTH) nor thyroxin (T₄) concentrations were associated with bone matrix IGF-I levels. To conclude, our study documented that in vivo long-term corticotherapy is associated with low trabecular human bone matrix IGF-I. In contrast, no influence of increased circulating parathyroid- or thyroid hormones levels on human iliac crest skeletal IGF-I concentrations was observed.

Key words

glucocorticoids - hormones - thyroid - autoimmunity - thyrotropin - hormones

References

• 1 Langdahl BL, Kassem M, Moller MK. et al . The effects of IGF-I and IGF-II on proliferation and differentiation of human osteoblasts and interactions with growth hormone.  Eur J Clin Invest. 1998;  28 176-183
• 2 Koch H, Jadlowiec JA, Campbell PG. Insulin-like growth factor-I induces early osteoblast gene expression in human mesenchymal stem cells.  Stem Cells Dev. 2005;  14 ((6)) 621-631
• 3 Noda T, Tokuda H, Yoshida M. et al . Possible involvement of phosphatidylinositol 3-kinase/Akt pathway in insulin-like growth factor-I-induced alkaline phosphatase activity in osteoblasts.  Horm Metab Res. 2005;  37 ((5)) 270-274
• 4 Nakayama Y, Nakajima Y, Kato N. et al . Insulin-like growth factor-I increases bone sialoprotein (BSP) expression through fibroblast growth factor-2 response element and homeodomain protein-binding site in the proximal promoter of the BSP gene.  J Cell Physiol. 2006;  208 ((2)) 326-335
• 5 Guicheux J, Heymann D, Rousselle AV. et al . Growth hormone stimulatory effects on osteoclastic resorption are partly mediated by insulin-like growth factor I: an in vitro study.  Bone. 1998;  22 ((1)) 25-31
• 6 Wang Y, Nishida S, Elalieh HZ. et al . Role of IGF-I signaling in regulating osteoclastogenesis.  J Bone Miner Res. 2006;  21 ((9)) 1350-1358
• 7 Seck T, Scheppach B, Scharla S. et al . Concentration of insulin-like growth factor (IGF)-I and -II in iliac crest bone matrix from pre- and postmenopausal women: relationship to age, menopause, bone turnover, bone volume, and circulating IGFs.  J Clin Endocrinol Metab. 1998;  83 ((7)) 2331-2337
• 8 Maccario M, Tassone F, Gauna C. et al . Effects of short-term administration of low-dose rhGH on IGF-I levels in obesity and Cushing's syndrome: indirect evaluation of sensitivity to GH.  Eur J Endocrinol. 2001;  144 ((3)) 251-256
• 9 Bang P, Degerblad M, Thorén M. et al . Insulin-like growth factor (IGF) I and II and IGF binding protein (IGFBP) 1, 2 and 3 in serum from patients with Cushing's syndrome.  Acta Endocrinol (Copenh). 1993;  128 ((5)) 397-404
• 10 Lakatos P, Foldes J, Nagy Z. et al . Serum insulin-like growth factor-I, insulin-like growth factor binding proteins, and bone mineral content in hyperthyroidism.  Thyroid. 2000;  10 ((5)) 417-423
• 11 Co Ng LL, Lang CH, Bereket A. et al . Effect of hyperthyroidism on insulin-like growth factor-I (IGF-I) and IGF-binding proteins in adolescent children.  J Pediatr Endocrinol Metab. 2000;  13 ((8)) 1073-1080
• 12 Iglesias P, Bayón C, Méndez J. et al . Serum insulin-like growth factor type 1, insulin-like growth factor-binding protein-1, and insulin-like growth factor-binding protein-3 concentrations in patients with thyroid dysfunction.  Thyroid. 2001;  11 ((11)) 1043-1048
• 13 Zimmermann-Belsing T, Juul Holst J, Feldt-Rasmussen U. The insulin-like growth factor axis in patients with autoimmune thyrotoxicosis: effect of antithyroid drug treatment.  Growth Horm IGF Res. 2004;  14 ((3)) 235-2344
• 14 Jehle PM, Ostertag A, Schulten K. et al . Insulin-like growth factor system components in hyperparathyroidism and renal osteodystrophy.  Kidney Int. 2000;  57 ((2)) 432-436
• 15 Pepene CE, Seck T, Diel I. et al . Concentration of insulin-like growth factor (IGF)-I in iliac crest bone matrix in premenopausal women with idiopathic osteoporosis.  Exp Clin Endocrinol Diabetes. 2004;  112 ((1)) 38-43
• 16 McCarthy TL, Ji C, Chen Y. et al . Time- and dose-related interactions between glucocorticoid and cyclic adenosine 3',5'-monophosphate on CCAAT/enhancer-binding protein-dependent insulin-like growth factor I expression by osteoblasts.  Endocrinology. 2000;  141 ((1)) 127-137
• 17 Pepene CE, Seck T, Diel I. et al . Influence of fluor salts, hormone replacement therapy and calcitonin on the concentration of insulin-like growth factor (IGF)-I, IGF-II and transforming growth factor-beta 1 in human iliac crest bone matrix from patients with primary osteoporosis.  Eur J Endocrinol. 2004;  150 ((1)) 81-91
• 18 Blum, W F, Ranke MB, Bierich JR. et al . Radioimmunoassay for IGFs and IGFBPs.  Growth Regulation. 1994;  4 ((Suppl 1)) 11-19
• 19 Dequeker J, Pearson J, Reeve J. et al . Dual X ray absorptiometry-cross-calibration and normative reference ranges for the spine: results of a European Community Concerted Action.  Bone. 1995;  17 247-254
• 20 Delany AM, Canalis E. Transcriptional repression of insulin-like growth factor I by glucocorticoids in rat bone cells.  Endocrinology. 1995;  136 4776-4781
• 21 Weinstein RS, Jilka RL, Parfitt AM. et al . Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone.  J Clin Invest. 1998;  102 ((2)) 274-282
• 22 O'Brien CA, Jia D, Plotkin LI. et al . Glucocorticoids act directly on osteoblasts and osteocytes to induce their apoptosis and reduce bone formation and strength.  Endocrinology. 2004;  145 ((4)) 1835-1841
• 23 Okazaki R, Riggs L, Conover CA. Glucocorticoid regulation of insulin-like growth factor-binding protein expression in normal human osteoblast-like cells.  Endocrinology. 1994;  134 126-132
• 24 Delany AM, Durant D, Canalis E. Glucocorticoid suppression of IGF-I transcription in osteoblasts.  Mol Endocrinol. 2001;  15 ((10)) 1781-1789
• 25 McCarthy TL, Centrella M, Canalis E. Parathyroid hormone enhances the transcript and polypeptide levels of insulin-like growth factor I in osteoblast-enriched cultures from fetal rat bone.  Endocrinology. 1989;  124 ((3)) 1247-1253
• 26 Pfeilschifter J, Laukhuf E, Muller-Beckmann B. et al . Parathyroid hormone increases the concentration of insulin-like growth factor-I and transforming growth factor beta-1 in rat bone.  J Clin Invest. 1995;  96 767-774
• 27 Watson P, Lazowski D, Han V. et al . Parathyroid hormone restores bone mass and enhances osteoblast insulin-like growth factor I gene expression in ovariectomized rats.  Bone. 1995;  16 ((3)) 357-365
• 28 Jilka RL. Molecular and cellular mechanisms of the anabolic effect of intermittent PTH.  Bone. 2007;  40 ((6)) 1434-1446
• 29 Pepene CE, Kasperk CH, Pfeilschifter J. et al . Effects of triiodothyronine on the insulin-like growth factor system in primary human osteoblastic cells in vitro.  Bone. 2001;  29 ((6)) 540-546

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