Wiener Klinische Wochenschrift

, Volume 116, Issue 1–2, pp 37–41 | Cite as

Bone metabolism during interferon-alpha treatment of essential thrombocythemia

  • Rajko Kusec
  • Vesna Kusec
  • Bettina Gisslinger
  • Wolfgang Woloszczuk
  • Heinz GisslingerEmail author
Original Article


In-vitro studies have demonstrated that interferon (IFN) has an inhibitory effect on bone formation. Changes in bone metabolism were investigated in 19 patients treated for essential thrombocythemia with IFN-alpha. Serum biochemical parameters of bone remodeling [total alkaline phosphatase, osteocalcin, type-1 procollagen carboxy-terminal propeptide (PICP). crosslinked telopeptide type-I collagen (ICTP)] and mineral metabolism (total calcium, inorganic phosphate, parathyroid hormone, 25-hydroxyvitamin D) were measured before and after long-term IFN-alpha treatment. The effects of the cumulative IFN-alpha dose and duration of therapy on biochemical markers of bone metabolism were analyzed. No uniform trend or pattern was observed in the measured biochemical parameters except for ICTP, which decreased after treatment. Correlations indicated modulation of bone metabolism, i.e. remodeling with suppression of resorption, as a consequence of therapy with IFN-alpha.

Key words

Interferon essential thrombocythemia myeloproliferative disorders bone biochemical markers 

Einfluss der Therapie mit Interferon-alpha auf den Knochenstoffwechsel bei der essentiellen Thrombozythämie


In-vitro-Studien haben gezeigt, dass Interferon (IFN) alpha die Knochenformation hemmt. Wir haben bei 19 Patienten mit essentieller Thrombozythämie vor und während der Interferontherapie die Veränderungen des Knochenstoffwechsels untersucht. Folgende biochemische Parameter des Knochenstoffwechsels wurden untersucht: Alkalische Phosphatase, Osteocalcin, Typ I Procollagen Carboxy-Terminal Propeptid (PICP), sowie cross-linked Telopeptid Typ I Collagen (ICTP) und Kalzium-Spiegel, anorganisches Phosphat, Parathormon, sowie 5-Hydroxy Cholecalciferol. Der Effekt der kumulativ verabreichten Interferon-Dosis und der Behandlungsdauer auf die biochemischen Knochenstoffwechselparameter wurde analysiert. Dabei wurde abgesehen von dem ICTP, das während der Behandlung abgenommen hat, kein einheitlicher Trend für die biochemischen Marker beobachtet. Die Korrelation der Knochenstoffwechselparameter vor und nach IFN alpha zeigte aber eine Veränderung des Knochenstoffwechsels mit vorwiegender Suppression der Knochenresorption während der Interferon-Therapie.


Interferon essentielle Thrombozythämie myeloproliferative Erkrankungen biochemische Marker des Knochenstoffwechsels. 


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  1. 1.
    Reilly JT, Barnett D, Dolan G, Forrest P, Eastham J, Smith A (1993) Characterization of an acute micromegakaryocytic leukaemia: evidence for the pathogenesis of myelofibrosis. Br J Heamatology 83: 58–62CrossRefGoogle Scholar
  2. 2.
    Gisslinger H, Ludwig H, Linkesch W, Chott A, Fritz E, Radaszkiewicz T (1989) Long-term interferon therapy for thrombocytosis in myeloproliferative diseases. Lancet 8639: 634–637CrossRefGoogle Scholar
  3. 3.
    Gisslinger H, Chott A, Scheithauer W, Gilly B, Linkesch W, Ludwig H (1991) Interferon in essential thrombocythemia. Br J Hematol 79 [Suppl 1]: 42–47CrossRefGoogle Scholar
  4. 4.
    Kasparu H, Bernhart M, Krieger O, Lutz D (1992) Remission may continue after termination of IFN alpha-2b treatment for essential thrombocythemia. Eur J Hematol 48: 33–36CrossRefGoogle Scholar
  5. 5.
    Sacchi S, Tabilio A, Leoni P, Riccardi A, Vecchi A, Messora C, et al (1993) Sustained complete hematological remission in essential thrombocythemia after discontinuation of long-term α-IFN treatment. Ann Hematol 66: 245–246CrossRefPubMedGoogle Scholar
  6. 6.
    Sacchi S, Kantarjian HM, Smith TL, O’Brien S, Pierce S, Kornblau S, et al (1998) Alfa-interferon in the treatment of essential thrombocythemia: clinical results and evaluation of its biological effects on the hematopoietic neoplastic clone. Italian Cooperative Group on ET. Leukemia 12: 289–294CrossRefPubMedGoogle Scholar
  7. 7.
    Gilbert HS (1998) Long-term treatment of myeloproliferative disease with Interferon alpha-2b. Cancer 83: 1205–1213CrossRefPubMedGoogle Scholar
  8. 8.
    Gisslinger H, Svoboda T, Clodi M, Gilly B, Ludwig H, Havelec L, et al (1993) Interferon-alpha stimulates the hypothalamic-pituitary adrenal axis in vivo and in vitro. Neuroendocrinology 57: 489–495CrossRefPubMedGoogle Scholar
  9. 9.
    Jimenez SA, Freundlich B, Rosenbloom J (1984) Selective inhibition of human diploid fibroblast collagen synthesis by interferons. J Clin Invest 74: 1112–1116CrossRefPubMedGoogle Scholar
  10. 10.
    Beresford JN, Taylor GT, Triffitt JT (1990) Interferons and bone. A comparison of the effects of interferon-α and interferon-λ in cultures of human bone-derived cells and an osteosarcoma cell line. Eur J Biochem 193: 589–597CrossRefPubMedGoogle Scholar
  11. 11.
    Oreffo RO, Romberg S, Virdi AS, Joyner CJ, Berven S, Triffitt JT (1999) Effects of interferon alpha on human osteoprogenitor cell growth and differentiation in vitro. J Cell Biochem 74: 372–385CrossRefPubMedGoogle Scholar
  12. 12.
    Shiozawa S, Tanaka Y, Morimoto I, Miyauchi A, Yammatani T, Fujita T (1989) Radioimmunoassay of circulating alpha-interferon with reference to aging and osteoporosis. Gerontology 35: 305–310CrossRefPubMedGoogle Scholar
  13. 13.
    Herrmann-Erlee MPM, Mulders M, van der Meer JM, van Zeeland JK, Loewi CWCM (1984) The effects of rat interferon on bone resorption and on the growth and differentiation of normal and transformed bone cells. Calc Tiss Int 36: S28Google Scholar
  14. 14.
    Christenson RH (1997) Biochemical markers of bone metabolism: an overview. Drugs Aging [Suppl 1]: 9–14Google Scholar
  15. 15.
    Aman MJ, Keller U, Derigs G, Mohamadzadeh M, Huber C, Peschel C (1994) Regulation of cytokine expression by interferon-α in human bone marrow stromal cells: inhibition of hematopoietic growth factors and induction of interleukin-1 receptor antagonist. Blood 84: 4142–4150PubMedGoogle Scholar
  16. 16.
    Goodman GR, Dissanayake IR, Gorodetsky E, Zhou H, Ma YF, Jee WSS, et al (1999) Interferon α unlike interferon λ, does not cause bone loss in the rat. Bone 25:459–463CrossRefPubMedGoogle Scholar
  17. 17.
    Miki T, Yoshida H, Nakatsuka K (1995) Effect of interferon-α on bone metabolism and bone mineral density. J Bone Miner Res 10 [Suppl 1]: S201Google Scholar
  18. 18.
    Perez Castrillon JL, Cano-Del Pozo M, Sanz-Izquierdo S, Velayos-Jimenez J, Dib-Wobakin W (2003) Bone mineral density in patients with multiple sclerosis: the effects of interferon. Rev Neurol 36: 901–903PubMedGoogle Scholar
  19. 19.
    Demers LM (1997) Clinical usefulness of markers of bone degradation and formation. Scand. J Clin Lab Invest 57 [Suppl 227]: 12–20Google Scholar
  20. 20.
    Russel RGG (1997) The assessment of bone metabolism in vivo using biochemical approaches. Horm Metab Res 29: 138–144CrossRefGoogle Scholar
  21. 21.
    Smalcelj R, Kusec V, Puretic Z, Marekovic Z (1998) Biochemical parameters of bone turnover in kidney transplant recipients. Wien Klin Wochenschr 110: 326–330PubMedGoogle Scholar
  22. 22.
    Kusec V, Kramaric M, Baric I, Stavljenic Rukavina A (1998) Osteocalcin and other serum bone biochemical markers in healthy population. Clinical Laboratory 44: 277–283Google Scholar
  23. 23.
    Kauppila M, Koskinen P, Pulkki K, Sonninen P, Remes K, Irjala K, et al (2000) Interferon-α treatment decreases serum cross-linked C-terminal Telopeptide of type I collagen in hematological diseases. Clin Lab Hem 22: 15–19CrossRefGoogle Scholar
  24. 24.
    Pousen LW, Melsen F, Bendix K (1998) A histomorphometric study of hematological disorders with respect to marrow fibrosis and osteosclerosis. APMIS 106: 495–499CrossRefGoogle Scholar
  25. 25.
    Futami E, Shioi A, Jono S, Inaba M, Nishizawa Y, Morii H (1995) Interferon-α can modulate the expression of parathyroid hormone receptor in human osteoblast-like cells. J Bone Miner Res 10 [Suppl 1]: S138Google Scholar

Copyright information

© Springer 2004

Authors and Affiliations

  • Rajko Kusec
    • 1
  • Vesna Kusec
    • 2
  • Bettina Gisslinger
    • 3
  • Wolfgang Woloszczuk
    • 4
  • Heinz Gisslinger
    • 3
    Email author
  1. 1.Institute of Clinical Chemistry and Department of MedicineUniversity Hospital “Merkur”ZagrebCroatia
  2. 2.Clinical Institute for Laboratory Diagnosis, Clinical Hospital Centre ZagrebUniversity of ZagrebZagrebCroatia
  3. 3.Division of Hematology and Blood Coagulation, Department of Internal Medicine 1University of Vienna, AKHViennaAustria
  4. 4.Ludwig Boltzmann Institute for Experimental EndocrinologyUniversity of ViennaViennaAustria

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