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Influence of glucocorticoid on bone in 3-, 6-, and 12-month-old rats as determined by bone mass and histomorphometry

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Modern Rheumatology

Abstract

The influence of glucocorticoid (GC) on bone in rats at different ages was investigated in order to provide insight into human glucocorticoid induced osteoporosis (GCOP). Three-, 6-, and 12-month-old female Wistar rats were divided into four groups: Zero-time control (ZT), vehicle (Cont), prednisolone (PSL) 2 mg/kg (P–L), PSL 20 mg/kg (P–H). PSL was subcutaneously administered every day for 4 weeks. Bone mineral density (BMD) at the proximal metaphysis and diaphysis of the tibia was measured by peripheral quantitative computed tomography. Histomorphometry of the tibia was performed for 3- and 6-month-old rats. GC increased trabecular and cortical BMD at the metaphysis in all 3-month-old rats with time. Trabecular BMD at the metaphysis in the P–L and P–H groups was significantly higher than in the control group. Histomorphometric parameters for both bone formation and resorption were also increased by GC treatment. In the 6-month-old rats, the metaphyseal trabecular BMD did not significantly change in any group, but the diaphyseal trabecular BMD significantly increased in the control group with time. The trabecular BMD of the metaphysis and diaphysis was significantly lower in the P–L and P–H groups than in the control group at week 4. Histomorphometric parameters for bone formation and resorption were both reduced by GC treatment. The BMD remained unchanged in all 12-month-old rats. Six-month-old rats treated with 20 mg/kg GC are suitable models for GC-induced osteoporosis with dominant cancellous bone decrease and reduced bone turnover. The pathology induced by 20 mg/kg prednisolone in 6-month-old female rats seems to be most similar to glucocorticoid-induced osteoporosis in humans.

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References

  1. Reid IR. Glucocorticoid osteoporosis-mechanisms and management. Eur J Endocrinol. 1997;137:209–17.

    Article  PubMed  CAS  Google Scholar 

  2. McHugh NA, Vercesi HM, Egan RW, Hey JA. In vivo rat assay: bone remodeling and steroid effects on juvenile bone by pQCT quantification in 7 days. Am J Physiol Endocrinol Metab. 2003;284:E70–E5.

    PubMed  CAS  Google Scholar 

  3. Lindgren JU, Merchant CR, De Luca HF. Effect of 1, 25-dihydroxyvitamin D3 on osteopenia induced by prednisolone in adult rats. Calcify Tissue Int. 1982;34:253–7.

    Article  CAS  Google Scholar 

  4. King CS, Weir EC, Gundberg CW, Fox J, Insogna KL. Effects of continuous glucocorticoid infusion on bone metabolism in the rat. Calcif Tissue Int. 1996;59:184–91.

    Article  PubMed  CAS  Google Scholar 

  5. Unoki E. Effect of human PTH on steroid-induced osteopenia: a histomorphometric study of decalcified and undercalcified trabecular bone sections in rat. Nippon Seikeigeka Gakkai Zasshi (J Jpn Orthop Assoc). 1995;69:1064–75 (in Japanese).

    CAS  Google Scholar 

  6. Hulley PA, Conradie MM, Langeveldt CR, Hough FS. Glucocorticoid-induced osteoporosis in the rat is prevented by the tyroisin phosphatase inhibitor, sodium orthovanadate. Bone. 2002;31(1):220–9.

    Article  PubMed  CAS  Google Scholar 

  7. Wimalawansa SJ, Chapa MT, Yallampalli C, Zhang R, Simmons DJ. Prevention of corticosteroid-induced bone loss with nitric oxide donor nitroglycerin in male rats. Bone. 1997;21:275–80.

    Article  PubMed  CAS  Google Scholar 

  8. Uzawa T, Hori M, Noda T, Takahashi H, Inoue J. Effect of prednisolone on bone metabolism in rats. In: Watanabe M, Yanagisawa M (eds) Kotsukeitaikeisoku (Quantitative analysis method of bone). Niigata, Nishimurashoten; 1986. p. 242–9 (in Japanese).

  9. Yamane I, Hagino H, Okano T, Enokida M, Yamasaki D, Teshima R. Effect of minodronic acid (ONO-5920) on bone mineral density and arthritis in adult rats with collagen-induced arthritis. Arthritis Rheum. 2003;48:1732–41.

    Article  PubMed  CAS  Google Scholar 

  10. Gasser JA. Assessing bone quantity by pQCT. Bone. 1995;17:145S–54S.

    PubMed  CAS  Google Scholar 

  11. Sato M. Comparative X-ray densitometry of bones from ovariectomized rats. Bone. 1995;17:157S–62S.

    PubMed  CAS  Google Scholar 

  12. Fukata S, Hagino H, Okano T, Yamane I, Kameyama Y, Teshima R. Effect of intermittent administration of human parathyroid hormone on bone mineral density and arthritis in rats with collagen-induced arthritis. Arthritis Rheum. 2004;50:4060–9.

    Article  PubMed  CAS  Google Scholar 

  13. Enokida M, Yamasaki D, Okano T, Hagino H, Morio Y, Teshima R. Bone mass changes of tibial and vertebral bones in young and adult rats with collagen- induced arthritis. Bone. 2001;28:87–93.

    Article  PubMed  CAS  Google Scholar 

  14. Yamasaki D, Enokida M, Okano T, Hagino H, Teshima R. Effects of ovariectomy and estrogen replacement therapy on arthritis and bone mineral density in rats with collagen-induced arthritis. Bone. 2001;28:634–40.

    Article  PubMed  CAS  Google Scholar 

  15. Hagino H, Kuraoka M, Kameyama Y, Okano T, Teshima R. Effect of a selective agonist for prostaglandin E receptor subtype EP4 (ONO-4819) on the cortical bone response to mechanical loading. Bone. 2005;36:444–53.

    Article  PubMed  CAS  Google Scholar 

  16. Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, et al. Bone histomorphometry: standardization of nomenclature, symbols, and units. J Bone Miner Res. 1987;2:595–610.

    PubMed  CAS  Google Scholar 

  17. Lukert BP, Raisz LG. Glucocorticoid-induced osteoporosis; pathogenesis and management. Ann Intern Med. 1990;112:352–64.

    PubMed  CAS  Google Scholar 

  18. Weinstein RS, Jilka RL, Parfitt AM, Manolagas SC. 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;102:274–82.

    Article  PubMed  CAS  Google Scholar 

  19. Tenenbaum HC, Heersche JN. Dexamethasone stimulates osteogenesis in chick periosteum in vitro. Endocrinology. 1985;117:2211–7.

    Article  PubMed  CAS  Google Scholar 

  20. Kaji H, Sugimoto T, Kanatani M, Nishiyama K, Chihara K. Dexamethasone stimulates osteoclast-like cell formation by directly acting on Hemo poietic blast cells and enhances osteoclast-like cell formation stimulated by parathyroid hormone and prostaglandin E2. J Bone Miner Res. 1997;12:734–41.

    Article  PubMed  CAS  Google Scholar 

  21. Nakamuta H, Nitta T, Hoshino T, Koida M. Glucocorticoid-induced osteopenia in rats: histomorphometrical and microarchitectural characterization and calcitonin effect. Biol Pharm Bull. 1996;19:217–9.

    PubMed  CAS  Google Scholar 

  22. Lindgren JU, Merchant CR, DeLuca HF. Effect of 1, 25-dihydroxyvitamin D3 on osteopenia induced by prednisolone in adult rats. Calcif Tissue Int. 1982;34:253–7.

    Article  PubMed  CAS  Google Scholar 

  23. Narita Y. Effect of intermittent administration of human PTH on experimental osteopenia in adult rat: a histomorphometric study of both trabecular and cortical bone of the vertebrae. Nippon Seikeigeka Gakkai Zasshi (J Jpn Orthop Assoc). 1995;69:1027–36. (in Japanese).

    CAS  Google Scholar 

  24. Wang Y, Ohtsuka M, Shao P, Sakamoto S, Shinoda H. Effects of methylprednisolone on bone formation and resorption in rats. Jpn J Pharmacol. 2002;90:236–46.

    Article  PubMed  CAS  Google Scholar 

  25. Wimalawansa SJ, Simmons DJ. Prevention of corticosteroid-induced bone loss with alendronate. Proc Soc Exp Biol Med. 1998;217:162–7.

    PubMed  CAS  Google Scholar 

  26. Ferretti JL, Gaffuri O, Capozza R, Cointry G, Bozzini CE, Olovera M, et al. Dexamethasone effects on mechanical, geometric and densitometric properties of rat femur diaphyses as described by peripheral quantitative computerized tomography and bending tests. Bone. 1995;16:119–24.

    Article  PubMed  CAS  Google Scholar 

  27. Dike N Kalu. The ovariectomized rat model of postmenopausal bone loss. Bone and Mineral 1991; 15:175–92.

  28. Godschalk MF, Downs RW. Effect of short-term glucocorticoids on serum osteocalcin in healthy young men. J Bone Miner Res. 1988;3:113–5.

    Article  PubMed  CAS  Google Scholar 

  29. Ton FN, Gunawardene SC, Lee H, Neer RM. Effects of low-dose prednisolone on bone metabolism. J Bone Miner Res. 2005;20:464–70.

    Article  PubMed  CAS  Google Scholar 

  30. Canalis E. Mechanisms of glucocorticoid action in bone: implications to glucocorticoid-induced osteoporosis. J Clin Endocrinol Metab. 1996;81:3441–7.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This research was supported in part by a grant-in-aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (17591573). We would like to express our sincere thanks to Mr. Kiichi Nonaka for his help with experiments. We also acknowledge the Niigata Bone Science Institute, especially Ms. Akemi Ito, for assistance in preparing sections and staining.

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Correspondence to Tomofumi Ogoshi.

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Ogoshi, T., Hagino, H., Fukata, S. et al. Influence of glucocorticoid on bone in 3-, 6-, and 12-month-old rats as determined by bone mass and histomorphometry. Mod Rheumatol 18, 552–561 (2008). https://doi.org/10.1007/s10165-008-0096-2

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  • DOI: https://doi.org/10.1007/s10165-008-0096-2

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