Clinical Rheumatology

, Volume 27, Issue 5, pp 565–572 | Cite as

Does low-dose and short-term glucocorticoids treatment increase the risk of osteoporosis in rheumatoid arthritis female patients?

  • Izabela Korczowska
  • Anna Olewicz-Gawlik
  • Jakub Trefler
  • Paweł Hrycaj
  • Jan Krzysztof Łącki
Original Article
First Online:
Received:
Revised:
Accepted:

Abstract

Rheumatoid arthritis (RA) is frequently complicated by peri-articular and generalized osteoporosis due to increased bone resorption by activated osteoclasts. Pro-inflammatory cytokines, such as TNF-alpha, interleukin 1 (IL1), and interleukin 6 (IL6) are thought, among other factors, to be directly responsible for this extra-articular complication of RA. Glucocorticoids (GCS) commonly prescribed in RA due to their strong anti-inflammatory effect are also well known for causing secondary osteoporosis during a prolonged use. An influence of low-dose GCS therapy (8.7 mg per day) on a bone turnover in female RA patients with or without previous history of GCS treatment was investigated by measuring bone mineral content (BMC), bone mineral density (BMD), and various biochemical markers of inflammation and bone metabolism in comparison to results obtained from: (1) RA patients who have not been treated with GCS and (2) the control group of healthy individuals. Sixty-two female patients with established active RA and 178 healthy individuals from the control group have been investigated. The RA patients were divided into three groups: 21 treated with GCS before the trial—these patients have continued GCS therapy using low doses during the observation; 21 with low-dose GCS therapy launched at the beginning of the trial; and 20 left without GCS treatment. All patients have been assessed twice: at the beginning and after 12 months of observation. BMC and BMD have been measured in all patients in a distal part of forearm. Additionally, several different biochemical markers of osteoporosis and inflammation have been determined.We did not notice any increase in bone metabolism between RA patients receiving GCS therapy for the first time and those treated without GCS after 12 months of observation. Results of BMC, BMD osteocalcin level, total and bone alkaline phosphatase, carboxy-terminal collagen cross links, carboxy-terminal propeptides of type 1 collagen, deoxypyridynoline, and calcium/creatinine ratio were comparable in both groups at the end of the study. There was a significant decrease of the level of IL-6 in patients who had GCS therapy launched at the beginning of observation (p < 0.01). However, levels of C-reactive protein (CRP) and α1-acid-glycoprotein (AGP) have not changed; the level of ESR dropped significantly (p < 0.05) in this group. In contrast, in the group of patients with the previous history of prolonged GCS treatment receiving low doses of GCS during the trial, statistically significant increase of CRP and AGP could be observed (p < 0.05) along with further significant worsening of the primary low BMD (p < 0.05).Based on the obtained data, we came to the conclusion that anti-inflammatory effect of the low-dose GCS therapy in RA patients without previous history of their use may balance their direct negative effect on BMC and BMD. In this group of RA patients, benefits resulting from the 12-month GCS therapy prevail over adverse effects, even if calcium with vitamin D3 supplementation, biphosphonians, or estrogens have not been introduced. On the other hand, low-dose GCS therapy could have no benefit for RA patients with the previous history of their prolonged use, as a rise of markers of inflammation and bone turnover, resulting in the further bone loss, has been observed.

Keywords

Glucocorticoids Markers of osteoporosis Osteoporosis Rheumatoid arthritis 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgment

There are no commercial or other associations that might pose a conflict of interest in connection with the submitted material.

References

  1. 1.
    Pincus T (1994) Rheumatoid arthritis: a medical emergency? Scand J Rheumatol 23:21–30CrossRefGoogle Scholar
  2. 2.
    Wolfe F, Mitchell DM, Sibley JT, Fries JF, Bloch DA, Williams CA, Spitz PW, Haga M, Kleinhexel SM, Cathey MA (1994) The mortality of rheumatoid arthritis. Arthritis Rheum 4:481–494CrossRefGoogle Scholar
  3. 3.
    Łącki JK, Sobieska M, Leszczynski P, Wiktorowicz K (1994) Microheterogenity of alpha 1-acid glycoprotein in rheumatoid arthritis patients treated with methotrexate. Ann Rheum Dis 53:480PubMedGoogle Scholar
  4. 4.
    Hamalainen H, Kautiainen H, Kaarela K, Kotaniemi A (2005) The development of bone mineral density and the occurrence of osteoporosis from 15 to 20 years of disease onset in patients with rheumatoid arthritis. Clin Exp Rheumatol. 23(2):193–198PubMedGoogle Scholar
  5. 5.
    Anon G (1993) Consensus development conference: diagnosis, prophilaxis, and treatment of osteoporosis. Am J Med 94:646–650CrossRefGoogle Scholar
  6. 6.
    Parfit AM (1983) The physiological and clinical significance of bone histomorphometric data. In: Recker R (ed) Bone histomorphometry, technics and interpretation. CRC Press, Boca Raton, pp 143–223Google Scholar
  7. 7.
    Fujita T, Matsui T, Nakao Y, Shiozawa S, Imai Y (1990) Cytokines and osteoporosis. Ann NY Acad Sci 587:371–375PubMedGoogle Scholar
  8. 8.
    Eriksen EF (1986) Normal and pathological remodelling of human trabecular bone: three dimensional reconstruction of the remodelling sequence in normal and in metabolic bone disease. Endocrine Rev 7:379–408CrossRefGoogle Scholar
  9. 9.
    Hall GM, Spector TD, Griffin AJ, Jawad AS, Hall ML, Doyle DV (1993) The effect of rheumatoid arthritis and steroides therapy on bone density in postmenopausal women. Arthritis Rheum 36:1510–1516PubMedCrossRefGoogle Scholar
  10. 10.
    Watts NB (1999) Clinical utility of biochemical markers of bone remodeling. Clin Chem 45:1359–1368PubMedGoogle Scholar
  11. 11.
    Armour KJ, Armour KE, van’t Hof RJ, Reid DM, Wei XQ, Liew FY, Ralston SH (2001) Activation of the inducible nitric oxide synthase pathway to inflammation-induced osteoporosis by supressing bone formation and causing osteoblast apoptosis. Arthritis Rheum 44(12):2790–2796PubMedCrossRefGoogle Scholar
  12. 12.
    Rico H, Herandez ER, Gomez-Castresana F, Yague M, Cabranes JA, Valor R (1990) Osteopenia in rheumatoid arthritis: a biochemical, hormonal and histmorphometric study. Clin Rheumatol 9:63PubMedCrossRefGoogle Scholar
  13. 13.
    Suzuki Y, Mizushima Y (1997) Osteoporosis and rheumatoid arthritis. Osteoporosis Int 7(Suppl 3):S217–22Google Scholar
  14. 14.
    Habib GS, Haj S (2005) Bone mineral density in patients with early rheumatoid arthritis treated with corticosteroids. Clin Rheumatol 24(2):129–133PubMedCrossRefGoogle Scholar
  15. 15.
    Tascioglu F, Colak O, Armagan O, Alatas O, Oner C (2005) The treatment of osteoporosis in patients with rheumatoid arthritis receiving glucocorticoids: a comparison of alendronate and intranasal salmon calcitonin. Rheumatol Int 26(1):21–29PubMedCrossRefGoogle Scholar
  16. 16.
    Roldan JF, Del Rincon I, Escalante A (2006) Loss of cortical bone from the metacarpal diaphysis in patients with rheumatoid arthritis: independent effects of systemic inflammation and glucocorticoids. J Rheumatol 33(3):508–516PubMedGoogle Scholar
  17. 17.
    Als OS, Christiansen C, Hellesen C (1984) Prevelance of decreased bone mass in rheumatoid arthritis. Relation to anti-inflammatory treatment. Clin Rheumatol 3:201–208PubMedCrossRefGoogle Scholar
  18. 18.
    Kroger H, Penttila IM, Alhava EM (1993) Low serum vitamin D metabolites in women with rheumatoid arthritis. Scand J Rheumatol 22:172PubMedCrossRefGoogle Scholar
  19. 19.
    Charles P, Poser JW, Mosekilde L, Jensen FT (1985) Estimation of bone turnover evaluated by 47 calcium kinetics: efficiency of serum bone gamma-carboxyglutamic acid containing protein, serum alkaline phosphatase and urinary hydroxyproline excertion. J Clin Invest 76:2254–2258PubMedCrossRefGoogle Scholar
  20. 20.
    Goldring MB, Birkhead JR, Suen LF, Yamin R, Mizuno S, Głowacki J, Abiser JL, Apperley JF (1994) Interleukin-1 β-modulated gene expression in immortalized human chondrocytes. J Clin Invest 94:2307–2316PubMedCrossRefGoogle Scholar
  21. 21.
    Bocquet J, Daireaux M, Langris M, Jouis V, Pujol JP, Beliard R, Loyau G (1986) Effect of a interleukin-1 like factor (mononuclear cell factor) on proteoglycan synthesis in cultured human articular chondrocytes. Biochem Biophys Res Commun 134:539–549PubMedCrossRefGoogle Scholar
  22. 22.
    Goldring MB, Birkhead JR, Sandell LJ, Kimura T, Krane SM (1988) Interleukin 1 suppresses expression of cartilage-specific types II and IX collagens and increases types I and III collagens in human chondrocytes. J Clin Invest 82:2026–2037PubMedCrossRefGoogle Scholar
  23. 23.
    Ishimi Y, Miyaura C, Jin CH, Akashu T, Abe E, Nakamura Y, Yamaguchi A, Yoshiki S, Matsuda T, Hirano T, Kishimoto T, Suda T (1990) IL-6 is produced by osteoblasts and induces bone resorption. J Immunol 145:3297–3303PubMedGoogle Scholar
  24. 24.
    Gertzbein SD, Lance EM (1976) The stimulation of lymphocytes by chondrocytes in mixed cultures. Clin Exp Immunol 24:102–109PubMedGoogle Scholar
  25. 25.
    Ralston SH, Russell RG, Gowen M (1990) Estrogen inhibits release of tumor necrosis factor from peripheral blood mononuclear cells in postmenopausal women. J Bone Miner Res 5:983–988PubMedCrossRefGoogle Scholar
  26. 26.
    Suda T, Udagawa N, Nakamura I, Miyaura C, Takahashi N (1995) Modulation of osteoclast differentiation by local factors. Bone 17:87S–91SPubMedCrossRefGoogle Scholar
  27. 27.
    Łącki JK (2000) Management of the patients with severe refractory rheumatoid arthritis: are the never treatment options worth considering. BioDrugs 13:425–435PubMedCrossRefGoogle Scholar
  28. 28.
    Łącki JK, Klama K, Mackiewicz SH, Mackiewicz U, Muller W (1995) Circulating interleukin-10 and intrleukin-6 serum levels in rheumatoid arthritis patients treated with methotrexate or gold salts. Preliminary report. Inflamm Res 44:24–26PubMedCrossRefGoogle Scholar
  29. 29.
    Oelzner P, Franke S, Muller A, Hein G, Stein G (1999) Relationship between soluble markers of immune activation and bone turnover in postmenopausal woman with rheumatoid arthritis. Rheumatology Oxford 38:841–847PubMedCrossRefGoogle Scholar
  30. 30.
    Butler RC, Davie MW, Worsfold M, Sharp CA (1991) Bone mineral content in patients with rheumatoid arthritis: relationship to low dose steroid therapy. Br J Rheumatol 30:86–90PubMedCrossRefGoogle Scholar
  31. 31.
    Olbright T, Benker G (1993) Glucocorticosteroid induced osteoporosis: pathogenesis, prevention and treatment with special regard to the rheumatic diseases. J Int Med 234:237CrossRefGoogle Scholar
  32. 32.
    Adachi DJ, Olszynski W, Hanley DA, Hodsman AB, Kendler DL, Siminoski KG, Brown J, Cowden EA, Goltzman D, Ioannidis G, Josse RG, Ste-Marie LG, Tenenhouse AM, Davison KS, Blocka KLN, Pollock P, Sibley J (2000) Management of corticosteroid-induced osteoporosis. Sem Arthr Rheum 4:228–251CrossRefGoogle Scholar
  33. 33.
    McLaughlin F, Mackintosh J, Hayes BP, McLaren A, Uings IJ, Salmon P, Humphreys J, Meldrum E, Farrow SN (2002) Glucocorticoid-induced osteopenia in the mouse as assessed by histomorphometry, microcomputed tomography, and biochemical markers. Bone 30(6):924–930PubMedCrossRefGoogle Scholar
  34. 34.
    Westhovens R, Dequeker J (2000) Rheumatoid arthritis and osteoporosis. Z Rheumatol 59(Suppl 1):33–38PubMedCrossRefGoogle Scholar
  35. 35.
    Cortet B, Flipo RM, Pigny P, Duquesnoy B, Racadot A, Boersma A, Delcambre B (1997) How useful are bone turnover markers in rheumatoid arthritis? Rev-Rhum 64:153–159Google Scholar
  36. 36.
    Gough A, Sambrook P, Devlin J, Huissoon A, Njeh C, Nguyen T, Emery P (1998) Osteoclastic activation is the principial mechanism leading to secondary osteoporosis in rheumatoid arthritis. J Rheumatol 25:1282–1289PubMedGoogle Scholar
  37. 37.
    Hakala M, Aman S, Luukkainen R, Risteli L, Kauppi M, Nieminen P, Risteli J (1995) Application of markers of collagen metabolism in serum and synovial fluid for assessment of disease process in patients with rheumatoid arthritis. Ann Rheum Dis 54:886–890PubMedCrossRefGoogle Scholar
  38. 38.
    Kroger H, Risteli J, Risteli L, Penttila I, Alhava E (1993) Serum osteocalcin and carboxyterminal propeptide of type I procollagen in rheumatoid arthritis. Ann Rheum Dis 52:338PubMedGoogle Scholar
  39. 39.
    Saag KG (2002) Glucocorticoid use in rheumatoid arthritis. Curr Rheumatol Rep 4(3):218–25PubMedCrossRefGoogle Scholar
  40. 40.
    Kollerup G, Hansen M, Horslev-Peterson K (1994) Urinary hydroxypyridinium cross-links of collagen in rheumatoid arthritis. Relation to disease activity and effects of methylprednisolone. Br J Rheumatol 33:816–820PubMedCrossRefGoogle Scholar
  41. 41.
    Bijlsma JW, Van Everdingen AA, Huisman M, De Nijs RN, Jacobs JW (2002) Glucocorticoids in rheumatoid arthritis: effects on erosions and bone. Ann N Y Acad Sci 966:82–90PubMedGoogle Scholar
  42. 42.
    van Everdingen AA, Jacobs JW, Siewertsz Van Reesema DR, Bijlsma JW (2002) Low-dose prednisone therapy for patients with early active rheumatoid arthritis: clinical efficiacy, disease-modifying properties, and side effects: a randomized, double-blind, placebo-controlled clinical trial. Ann Intern Med 136(1):1–12PubMedGoogle Scholar
  43. 43.
    Laan RF, Jansen TL, van Riel PL (1999) Glucocorticosteroides in the management of rheumatoid arthristis. Rheumatology 38:6PubMedCrossRefGoogle Scholar
  44. 44.
    van Everdingen AA, Siewertsz Van Reesema DR, Jacobs JW, Bijlsma JW (2003) Low dose glucocorticoids in early rheumatoid arthritis: discordant effects on bone mineral density and fractures? Clin Exp Rheumatol 21:145–147Google Scholar

Copyright information

© Clinical Rheumatology 2007

Authors and Affiliations

  • Izabela Korczowska
    • 1
  • Anna Olewicz-Gawlik
    • 1
  • Jakub Trefler
    • 2
  • Paweł Hrycaj
    • 1
  • Jan Krzysztof Łącki
    • 2
  1. 1.Department of Rheumatology and Clinical ImmunologyUniversity of Medical Sciences in PoznańPoznańPoland
  2. 2.Department of Rheumatoid DiseasesInstitute of Rheumatology in WarsawWarszawaPoland

Personalised recommendations