Advertisement

Journal of Bone and Mineral Metabolism

, Volume 36, Issue 6, pp 628–639 | Cite as

Effect of prednisone treatment for 30 and 90 days on bone metabolism in collagen-induced arthritis (CIA) rats

  • Xinle Zhang
  • Xuna Wu
  • Yalin Min
  • Jiaqi Lu
  • Xuemei Zhang
  • Wenshuang Chen
  • Liyi Zou
  • Xiaohua Lv
  • Liao Cui
  • Bilian Xu
Original Article
  • 132 Downloads

Abstract

Glucocorticoids (GCs) are often prescribed to treat rheumatoid arthritis (RA) in the long term, but there is still controversy in the administration of GCs, mainly because of the adverse reactions such as osteoporosis. Numerous studies have demonstrated that osteoporosis could be induced by GCs in normal rats. However, few experiments have focused on whether osteoporosis could be induced or aggravated by GCs in collagen induced arthritis (CIA) rats. We have investigated bone changes in CIA rats treated with prednisone at 4.5 mg/kg/day for 30 and 90 days by bone histomorphometry, bone mineral density (BMD), micro-CT, biomechanical test, and enzyme-linked immunosorbant assay. We found that high bone turnover osteoporosis was shown in CIA rats. Prednisone treatment for 30 and 90 days improved articular structure and decelerated the degeneration of the femur in CIA rats, but did not improve BMD and bone biomechanics. We conclude that osteoporosis was not aggravated in CIA rats treated with prednisone for 30 and 90 days. On the contrary, prednisone treatment for 30 and 90 days could prevent bone loss of the femur in CIA rats. There was a negative effect on bone metabolism in CIA rats treated with prednisone for 90 days.

Keywords

Rheumatoid arthritis Osteroporosis Prednisone Collagen-induced arthritis Rats 

Notes

Acknowledgements

This study was supported by grants from the National Natural Science Foundation of China (no. 81373499), the Science and Technology Foundation of Zhanjiang, Guangdong province, China (no. 201018003).

Compliance with ethical standards

Conflict of interest

Xinle Zhang, Xuna Wu, Yalin Min, Jiaqi Lu, Xuemei Zhang, Wenshuang Chen, Liyi Zou, Xiaohua Lv, Liao Cui and Bilian Xu declare that they have no conflicts of interest.

Human and animal rights and informed consent

All animal experiments were approved by the Academic Committee on the Ethics of Animal Experiments of the Guangdong Medical University, Zhanjiang, China. Permit number: SCXK(Beijing)2012-001.

References

  1. 1.
    van Everdingen AA, Siewertsz VRD, Jacobs JW, Bijlsma JW (2003) Low-dose glucocorticoids in early rheumatoid arthritis: discordant effects on bone mineral density and fractures? Clin Exp Rheumatol 21:155–160PubMedGoogle Scholar
  2. 2.
    den Uyl D, van Raalte DH, Nurmohamed MT, Lems WF, Bijlsma JW, Hoes JN, Dijkmans BA, Diamant M (2012) Metabolic effects of high-dose prednisolone treatment in early rheumatoid arthritis: balance between diabetogenic effects and inflammation reduction. Arthritis Rheum 64:639–646CrossRefGoogle Scholar
  3. 3.
    Bae SC, Corzillius M, Kuntz KM, Liang MH (2003) Cost-effectiveness of low dose corticosteroids versus non-steroidal anti-inflammatory drugs and COX-2 specific inhibitors in the long-term treatment of rheumatoid arthritis. Rheumatology (Oxford) 42:46–53CrossRefGoogle Scholar
  4. 4.
    van Everdingen AA, Jacobs JW, Siewertsz VRD, Bijlsma JW (2002) Low-dose prednisone therapy for patients with early active rheumatoid arthritis: clinical efficacy, disease-modifying properties, and side effects: a randomized, double-blind, placebo-controlled clinical trial. Ann Intern Med 136:1–12CrossRefGoogle Scholar
  5. 5.
    Wu Q, Xiong X, Zhang X, Lu J, Zhang X, Chen W, Wu T, Cui L, Liu Y, Xu B (2016) Secondary osteoporosis in collagen-induced arthritis rats. J Bone Miner Metab 34:500–516CrossRefGoogle Scholar
  6. 6.
    Brand DD, Latham KA, Rosloniec EF (2007) Collagen-induced arthritis. Nat Protoc 2:1269–1275CrossRefGoogle Scholar
  7. 7.
    Sajti E, van Meeteren N, Kavelaars A, van der Net J, Gispen WH, Heijnen C (2004) Individual differences in behavior of inbred Lewis rats are associated with severity of joint destruction in adjuvant-induced arthritis. Brain Behav Immun 18:505–514CrossRefGoogle Scholar
  8. 8.
    Lubberts E, Koenders MI, Oppers-Walgreen B, van den Bersselaar L, Coenen-de RC, Joosten LA, van den Berg WB (2004) Treatment with a neutralizing anti-murine interleukin-17 antibody after the onset of collagen-induced arthritis reduces joint inflammation, cartilage destruction, and bone erosion. Arthritis Rheum 50:650–659CrossRefGoogle Scholar
  9. 9.
    Douni E, Sfikakis PP, Haralambous S, Fernandes P, Kollias G (2004) Attenuation of inflammatory polyarthritis in TNF transgenic mice by diacerein: comparative analysis with dexamethasone, methotrexate and anti-TNF protocols. Arthritis Res Ther 6:R65–R72CrossRefGoogle Scholar
  10. 10.
    Vidal B, Cascao R, Vale AC, Cavaleiro I, Vaz MF, Brito JA, Canhao H, Fonseca JE (2015) Arthritis induces early bone high turnover, structural degradation and mechanical weakness. PLoS ONE 10:e117100Google Scholar
  11. 11.
    Takagi T, Tsao PW, Totsuka R, Suzuki T, Murata T, Takata I (1998) Dexamethasone prevents the decrease of bone mineral density in type II collagen-induced rat arthritis model. Jpn J Pharmacol 78:225–228CrossRefGoogle Scholar
  12. 12.
    Hickling P, Jacoby RK, Kirwan JR (1998) Joint destruction after glucocorticoids are withdrawn in early rheumatoid arthritis. Arthritis and Rheumatism Council Low Dose Glucocorticoid Study Group. Br J Rheumatol 37:930–936CrossRefGoogle Scholar
  13. 13.
    Kroot EJ, Huisman AM, Van Zeben J, Wouters JM, Van Paassen HC (2006) Oral pulsed dexamethasone therapy in early rheumatoid arthritis: a pilot study. Ann N Y Acad Sci 1069:300–306CrossRefGoogle Scholar
  14. 14.
    Buttgereit F, Mehta D, Kirwan J, Szechinski J, Boers M, Alten RE, Supronik J, Szombati I, Romer U, Witte S, Saag KG (2013) Low-dose prednisone chronotherapy for rheumatoid arthritis: a randomised clinical trial (CAPRA-2). Ann Rheum Dis 72:204–210CrossRefGoogle Scholar
  15. 15.
    Engvall IL, Svensson B, Boonen A, van der Heijde D, Lerner UH, Hafstrom I (2013) Low-dose prednisolone in early rheumatoid arthritis inhibits collagen type I degradation by matrix metalloproteinases as assessed by serum 1CTP—a possible mechanism for specific inhibition of radiological destruction. Rheumatology (Oxford) 52:733–742CrossRefGoogle Scholar
  16. 16.
    Kirwan JR (1995) The effect of glucocorticoids on joint destruction in rheumatoid arthritis. The Arthritis and Rheumatism Council Low-Dose Glucocorticoid Study Group. N Engl J Med 333:142–146CrossRefGoogle Scholar
  17. 17.
    Gotzsche PC, Johansen HK (1998) Meta-analysis of short-term low dose prednisolone versus placebo and non-steroidal anti-inflammatory drugs in rheumatoid arthritis. BMJ 316:811–818CrossRefGoogle Scholar
  18. 18.
    Lems WF, Gerrits MI, Jacobs JW, van Vugt RM, van Rijn HJ, Bijlsma JW (1996) Changes in (markers of) bone metabolism during high dose corticosteroid pulse treatment in patients with rheumatoid arthritis. Ann Rheum Dis 55:288–293CrossRefGoogle Scholar
  19. 19.
    Neeck G, Kluter A, Dotzlaw H, Eggert M (2002) Involvement of the glucocorticoid receptor in the pathogenesis of rheumatoid arthritis. Ann N Y Acad Sci 966:491–495CrossRefGoogle Scholar
  20. 20.
    Goecke A, Guerrero J (2006) Glucocorticoid receptor beta in acute and chronic inflammatory conditions: clinical implications. Immunobiology 211:85–96CrossRefGoogle Scholar
  21. 21.
    Manenschijn L, van den Akker EL, Lamberts SW, van Rossum EF (2009) Clinical features associated with glucocorticoid receptor polymorphisms. An overview. Ann N Y Acad Sci 1179:179–198CrossRefGoogle Scholar
  22. 22.
    Cavalcante LO, Melo MR, Dinis VG, Castro RB, Souza BD, Longui CA (2010) Quantitation of glucocorticoid receptor alpha and NF-kappaB pathway mRNA and its correlation with disease activity in rheumatoid arthritis patients. Genet Mol Res 9:2300–2310CrossRefGoogle Scholar
  23. 23.
    Earp JC, Dubois DC, Molano DS, Pyszczynski NA, Keller CE, Almon RR, Jusko WJ (2008) Modeling corticosteroid effects in a rat model of rheumatoid arthritis I: mechanistic disease progression model for the time course of collagen-induced arthritis in Lewis rats. J Pharmacol Exp Ther 326:532–545CrossRefGoogle Scholar
  24. 24.
    Earp JC, Dubois DC, Molano DS, Pyszczynski NA, Almon RR, Jusko WJ (2008) Modeling corticosteroid effects in a rat model of rheumatoid arthritis II: mechanistic pharmacodynamic model for dexamethasone effects in Lewis rats with collagen-induced arthritis. J Pharmacol Exp Ther 326:546–554CrossRefGoogle Scholar
  25. 25.
    Ishida O, Furuya T, Inoue E, Ochi K, Ikari K, Taniguchi A, Yamanaka H, Momohara S (2015) Risk factors for established vertebral fractures in Japanese patients with rheumatoid arthritis: results from a large prospective observational cohort study. Mod Rheumatol 25:373–378CrossRefGoogle Scholar
  26. 26.
    Pereira RM, Delany AM, Canalis E (2001) Cortisol inhibits the differentiation and apoptosis of osteoblasts in culture. Bone 28:484–490CrossRefGoogle Scholar
  27. 27.
    Smith E, Coetzee GA, Frenkel B (2002) Glucocorticoids inhibit cell cycle progression in differentiating osteoblasts via glycogen synthase kinase-3beta. J Biol Chem 277:18191–18197CrossRefGoogle Scholar
  28. 28.
    Warriner AH, Saag KG (2013) Prevention and treatment of bone changes associated with exposure to glucocorticoids. Curr Osteoporos Rep 11:341–347CrossRefGoogle Scholar
  29. 29.
    Hofbauer LC, Kuhne CA, Viereck V (2004) The OPG/RANKL/RANK system in metabolic bone diseases. J Musculoskelet Neuronal Interact 4:268–275PubMedGoogle Scholar
  30. 30.
    Giner M, Rios MA, Montoya MA, Vazquez MA, Naji L, Perez-Cano R (2009) RANKL/OPG in primary cultures of osteoblasts from post-menopausal women. Differences between osteoporotic hip fractures and osteoarthritis. J Steroid Biochem Mol Biol 113:46–51CrossRefGoogle Scholar
  31. 31.
    Yasuda H (2013) RANKL, a necessary chance for clinical application to osteoporosis and cancer-related bone diseases. World J Orthop 4:207–217CrossRefGoogle Scholar

Copyright information

© The Japanese Society for Bone and Mineral Research and Springer Japan KK 2017

Authors and Affiliations

  • Xinle Zhang
    • 1
  • Xuna Wu
    • 1
  • Yalin Min
    • 1
  • Jiaqi Lu
    • 1
    • 2
  • Xuemei Zhang
    • 1
  • Wenshuang Chen
    • 1
  • Liyi Zou
    • 1
  • Xiaohua Lv
    • 1
  • Liao Cui
    • 1
  • Bilian Xu
    • 1
  1. 1.Department of Pharmacology, Guangdong Key Laboratory for Research and Development of Natural DrugsGuangdong Medical UniversityZhanjiangChina
  2. 2.Department of PharmacyHuizhou First People’s HospitalHuizhouChina

Personalised recommendations