Skip to main content
SpringerLink
Log in

Short-term effects of glucocorticoid therapy on biochemical markers of bone metabolism in Japanese patients: a prospective study

  • Original Article
  • Published:
Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

Glucocorticoid (GC) therapy induces rapid bone loss, but the early changes in calcium and bone metabolism in patients treated with GC have not been clarified. To investigate the changes in calcium and bone metabolism during the early stage of GC therapy, we analyzed various biochemical markers of bone metabolism. The serum levels of calcium (Ca), phosphorus, parathyroid hormone (PTH), osteocalcin (OC), bone alkaline phosphatase (BAP), and type I collagen cross-linked N-telopeptide (NTx), as well as the urinary levels of Ca, creatinine, and NTx, were measured on days 0, 3, 7, and 28 of GC therapy. The subjects were divided into the following four groups: 9 patients receiving pulse therapy (P), 18 patients receiving prednisolone (PSL) at doses ≥40 mg/day (H), 9 patients receiving PSL at doses ≥20 mg/day (M), and 11 patients receiving PSL at doses ≤10 mg/day (S). The serum OC level showed a marked decrease on day 3 of GC therapy (−41.2% ± 6.6%, P < 0.01), while the BAP level decreased gradually. Both serum and urinary NTx levels significantly increased on day 7 of GC therapy (9.9% ± 4.5%, P < 0.05, and 42.2% ± 10.6%, P < 0.01, respectively). Urinary Ca excretion was increased on day 3 of GC therapy and continued to increase until 4 weeks, while intact PTH showed an increase on day 3 and then remained constant until 4 weeks. In groups P and H, there were significant early changes in OC, BAP, NTx, and intact PTH levels, as well as urinary Ca excretion. Even a PSL dose of <10 mg/day caused a decrease in the serum OC level. In conclusion, the biochemical markers of Ca and bone metabolism showed different kinetics depending on the dose of GC, and it is important for patients on high-dose GC therapy to receive prophylaxis for bone loss from the start of GC treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Buttgereit F, Straub RH, Wehling M, Burmester GR (2004) Glucocorticoids in the treatment of rheumatic diseases. Arthritis Rheum 50:3408–3417

    Article  PubMed  CAS  Google Scholar 

  2. Tappy L, Randin D, Volleweidr P, Paquot N, Scherrer U, Schniter P, et al (1994) Mechanism of dexamethasone-induced insulin resistance in healthy humans. J Clin Endocrinol Metab 79:1063–1069

    Article  PubMed  CAS  Google Scholar 

  3. Vann Staa TP, Leufkens HGM, Abenhaim L, Zhang B, Cooper C (2000) Use of oral corticosteroids and risk of fractures. J Bone Miner Res 15:993–1000

    Article  Google Scholar 

  4. Manolagas SC, Weinstein RS (1999) Developments in the pathogenesis and treatment of steroid-induced osteoporosis. J Bone Miner Res 14:1061–1066

    Article  PubMed  CAS  Google Scholar 

  5. Buttgereit F, Wehling M, Burmester GR (1998) A new hypothesis of modular glucocorticoid actions. Steroid treatment of rheumatic diseases revisited. Arthritis Rheum 41:761–767

    Article  PubMed  CAS  Google Scholar 

  6. Kuroki Y, Takabayashi C, Nishiyama K, Shimada T, Shiozawa S, Chihara K, Ueba Y (2004) Adrenocorticotropic hormone response to hypoglycemic stress was preserved by a single bedtime 3-mg dose of prednisolone in patients with rheumatoid arthritis. Mod Rheumatol 14:291–295

    Article  CAS  Google Scholar 

  7. Buttgereit F, da Silva JA, Boers M, Burmester GR, Cutolo M, et al (2002) Standardised nomenclature for glucocorticoid dosages and glucocorticoid treatment regimens: current questions and tentative answers in rheumatology. Ann Rheum Dis 61:718–722

    Article  PubMed  CAS  Google Scholar 

  8. Garnero P, Hausherr E, Chaupuy MC, Marcelli C, Grandjean H, et al (1996) Markers of bone resorption predict hip fracture in elderly women: EPIDOS prospective study. J Bone Miner Res 11:1531–1538

    PubMed  CAS  Google Scholar 

  9. Garnero P, Sornay-Rendu E, Claustrar B, Delmas PD (2000) Biochemical markers of bone turnover, endogenous hormones and the risk of fracture in postmenopausal women: the OFELY study. J Bone Miner Res 15:1526–1536

    Article  PubMed  CAS  Google Scholar 

  10. Korakaki E, Gourgiotis D, Aligizakis A, Manoura A, Hatzidaki E, et al (2007) Levels of bone collagen markers in preterm infants: relation to antenatal glucocorticoid treatment. J Bone Miner Metab 25:172–178

    Article  PubMed  CAS  Google Scholar 

  11. Christiansen C, Riis BJ, Rodbro P (1987) Prediction of rapid bone loss in postmenopausal women. Lancet 1(8542):1105–1108

    Article  PubMed  CAS  Google Scholar 

  12. Gomez B, Ardakani S, Ju J, Jenkins D, Cerelli MJ, et al (1995) Monoclonal antibody assay for measuring bone-specific alkaline phosphatase activity in serum. Clin Chem 41:1560–1566

    PubMed  CAS  Google Scholar 

  13. Blackburn GF, Shah HP, Kenten JH, Leland J, Kamin RA, et al (1991) Electrochemiluminescence detection for development of immunoassay and DNA probe assays for clinical diagnosis. Clin Chem 37:1534–1539

    PubMed  CAS  Google Scholar 

  14. Woitage HW, Pecherstorfer M, Li Y, Keck AV, Horn E, et al (1999) Novel serum markers of bone resorption: clinical assessment and comparison with established urinary indices. J Bone Miner Res 14:792–801

    Article  Google Scholar 

  15. Godschalk MF, Down RW (1988) Effects of short-term glucocorticoids on serum osteocalcin in healthy young men. J Bone Miner Res 3:113–115

    PubMed  CAS  Google Scholar 

  16. Purummel MF, Wiersinga WM, Lips P, Sanders TB, Sauerwein HP (1991) The course of biochemical parameters of bone turnover during treatment with corticosteroids. J Clin Endocrinol Metab 72:382–386

    Google Scholar 

  17. Pearce G, Tabensky A, Dermas PD, et al (1998) Corticosteroidinduced bone loss in men. J Clin Endocrinol Metab 83:801–806

    Article  PubMed  CAS  Google Scholar 

  18. Dovio A, Perazzolo L, Osella G, Ventura M, Termine A, et al (2004) Immediate fall of bone formation and transient increase of bone resorption in the course of high-dose, short-term glucocorticoid therapy in young patients with multiple sclerosis. J Clin Endocrinol Metab 89:4923–4928

    Article  PubMed  CAS  Google Scholar 

  19. Webster JC, Cidlowski JA (1999) Mechanisms of glucocorticoidreceptor mediated repression of gene expression. Trends Endocrinol Metab 10:396–402

    Article  PubMed  CAS  Google Scholar 

  20. Walton RJ, Preston CJ, Russell RCG, Kenis JA (1975) An estimate of the turnover rate of bone-derived plasma alkaline phosphatase in Paget’s disease. Clin Chim Acta 63:227–229

    Article  PubMed  CAS  Google Scholar 

  21. Weinstein RS, Chen JR, Powers CC, Stewert SA, Landes RD, et al (2002) Promotion of osteoclast survival and antagonism of bisphosphonate induced osteoclast apoptosis by glucocorticoids. J Clin Invest 109:1041–1048

    PubMed  CAS  Google Scholar 

  22. Weinstein RS, Jilka RL, Parfitt AM, Manolagas SC (1998) Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. J Clin Invest 102:274–282

    Article  PubMed  CAS  Google Scholar 

  23. Rubin MR, Bilezikian JP (2002) Clinical review 151. The role of parathyroid hormone in the pathogenesis of glucocorticoid-induced osteoporosis: a reexamination of the evidence. J Clin Endocrinol Metab 87:4033–4041

    Article  PubMed  CAS  Google Scholar 

  24. Paz-Pacheco E, Fuleihan GE, Leboff MS (1995) Intact parathyroid hormone levels are not elevated in glucocorticoid-treated subjects. J Bone Miner Res 10:1713–718

    Article  PubMed  CAS  Google Scholar 

  25. Hattersley AT, Meeran K, Burran J, Hill P, Shiner R (1994) The effect of long-term and short-term corticosteroids on plasma calcitonin and parathyroid hormone levels. Calcif Tissue Int 54:198–202

    Article  PubMed  CAS  Google Scholar 

  26. Sugimoto T, Brown AJ, Ritter C, Morrissey J, Slatopolsky E, Martin KJ (1989) Combined effects of dexamethasone and 1,25-dihydroxyvitamin D3 on parathyroid hormone secretion in cultured bovine parathyroid cells. Endocrinology 125:638–641

    PubMed  CAS  Google Scholar 

  27. Lems WF, Gerrits MI, Jacobs JWG, van Vugt RM, van Rijin HJM, Bijlsma JWJ (1996) Changes in markers of bone metabolism during high dose corticosteroid pulse treatment in patients with rheumatoid arthritis. Ann Rheum Dis 55:288–293

    Article  PubMed  CAS  Google Scholar 

  28. Frediani B, Falsetti P, Bisogno S, Baldi F, Acciai C, et al (2004) Effects of high dose methylprednisolone pulse therapy on bone mass and biochemical markers of arthritis: a 12-month randomized prospective controlled study. J Rheumatol 31:1083–1087

    PubMed  CAS  Google Scholar 

  29. Chaki O, Yoshikata I, Kikuchi R, Nakayama M, Uchiyama Y, et al (2000) The predictive value of biochemical markers of bone turnover for bone mineral density in postmenopausal Japanese women. J Bone Miner Res 15:1537–1544

    Article  PubMed  CAS  Google Scholar 

  30. Iki M, Kajita E, Dohi Y, Nishino H, Kusaka Y, et al (1996) Age, menopause, bone turnover markers and lumbar bone loss in healthy Japanese women. Maturitas 25:59–67

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Internal Medicine, Kobe Century Memorial Hospital, 1-9-1 Misakicho, Hyogo-ku, Kobe, 652-0855, Japan

    Yasuo Kuroki

  2. Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan

    Hiroshi Kaji

  3. Clinical Laboratory, Kobe University Hospital, Kobe, Japan

    Seiji Kawano

  4. Neurology, Kobe University Hospital, Kobe, Japan

    Fumio Kanda

  5. Internal Medicine, Kobe Rehabilitation Hospital, Kobe, Japan

    Yutaka Takai

  6. Internal Medicine, Yodogawa Christian Hospital, Osaka, Japan

    Michiko Kajikawa

  7. Internal Medicine 1, Shimane University Faculty of Medicine, Izumo, Japan

    Toshitsugu Sugimoto

Authors
  1. Yasuo Kuroki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hiroshi Kaji
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Seiji Kawano
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fumio Kanda
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yutaka Takai
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Michiko Kajikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Toshitsugu Sugimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yasuo Kuroki.

About this article

Cite this article

Kuroki, Y., Kaji, H., Kawano, S. et al. Short-term effects of glucocorticoid therapy on biochemical markers of bone metabolism in Japanese patients: a prospective study. J Bone Miner Metab 26, 271–278 (2008). https://doi.org/10.1007/s00774-007-0821-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00774-007-0821-5

Key words

Search

Navigation