European Radiology

, Volume 18, Issue 5, pp 1005–1011 | Cite as

Dynamic contrast-enhanced MRI in Paget’s disease of bone–correlation of regional microcirculation and bone turnover

  • M. LibicherEmail author
  • C. Kasperk
  • M. Daniels
  • W. Hosch
  • H.-U. Kauczor
  • S. Delorme


The purpose of this study was to evaluate regional microcirculation in Paget’s disease of bone (PD) with dynamic contrast-enhanced MR imaging (DCE-MRI). Additionally, we correlated regional bone perfusion with alkaline phosphatase as serum marker of bone turnover. We examined 71 patients with PD (27 men, 44 women, 67±10 years) localized at the axial and appendicular skeleton. Contrast uptake was analyzed using a two-compartment model with the output variables amplitude A and exchange rate constant kep. Color-coded parametric images were generated to visualize microcirculation. Serum levels of alkaline phosphatase (AP) were compared with DCE-MRI parameters. Amplitude A and exchange rate constant kep were significantly increased in PD compared to unaffected bone (APD 0.81±0.24 vs. Acontrol 0.34±0.1 and kep PD 4.0±2.86 vs. kep control 1.73±0.88, p<0.001). There was a significant correlation (rs=0.5–0.7) of DCE-MRI parameters and AP at the axial (pelvis, spine) and appendicular skeleton (femur, tibia). The long bones showed increased circulation of the advancing peripheral zones and no vascularization of the central part, which had been replaced by fatty tissue. Regional microcirculation in PD is inhomogeneous with focal areas of excessive hypervascularity, especially in the advancing peripheral zone. There is a significant correlation of bone circulation and bone turnover in PD. DCE-MRI might therefore be a diagnostic tool for monitoring therapeutic effects of bisphoshonates in Paget’s disease of bone.


Osteitis deformans Magnetic resonance imaging Microcirculation 


  1. 1.
    Roodman GD, Windle JJ (2005) Paget disease of bone. J Clin Invest 115:200–208PubMedGoogle Scholar
  2. 2.
    Anderson DC (2001) Paget’s disease of bone is characterized by excessive bone resorption coupled with excessive and disorganized bone formation. Bone 29:292–293PubMedCrossRefGoogle Scholar
  3. 3.
    Smith SE, Murphey MD, Motamedi K, Mulligan ME, Resnik CS, Gannon FH (2002) From the archives of the AFIP. Radiologic spectrum of Paget disease of bone and its complications with pathologic correlation. Radiographics 22:1191–1216PubMedGoogle Scholar
  4. 4.
    Resnick D (2002) Paget’s disease. In: Resnick D (ed) Diagnosis of bone and joint disorders, 4th edn. WB Saunders, Philadelphia, pp 1947–2000Google Scholar
  5. 5.
    Arlet J, Mazieres B (1975) Circulation in bone in Paget’s disease. General review and personal results. Rev Rhum Mal Osteoartic 42:643–646Google Scholar
  6. 6.
    Demmler K (1974) Die Vaskularisation des Paget-Knochens. Dtsch Med Wochenschr 99:91–95PubMedCrossRefGoogle Scholar
  7. 7.
    Alvarez L, Guanabens N, Peris P et al (2001) Usefulness of biochemical markers of bone turnover in assessing response to the treatment of Paget’s disease. Bone 29:447–452PubMedCrossRefGoogle Scholar
  8. 8.
    Storsteen KA, Janes JM (1954) Arteriography and vascular studies in Paget’s disease of bone. J Am Med Ass 154:472–474Google Scholar
  9. 9.
    Rongstad KM, Wheeler DL, Enneking WF (1994) A comparison of the amount of vascularity in pagetic and normal human bone. Clin Orthop Relat Res 306:247–249PubMedGoogle Scholar
  10. 10.
    Loneragan R (1999) Digital subtraction angiography demonstration of bone hypervascularity in Paget’s disease. Australas Radiol 43:260–261PubMedCrossRefGoogle Scholar
  11. 11.
    Heistad DD, Abboud FM, Schmid PG, Mark AL, Wilson WR (1975) Regulation of blood flow in Paget’s disease of bone. J Clin Invest 55:69–74PubMedCrossRefGoogle Scholar
  12. 12.
    Wootton R, Tellez M, Green JR, Reeve J (1981) Skeletal blood flow in Paget’s disease of bone. Metab Bone Dis Relat Res 3:263–270PubMedCrossRefGoogle Scholar
  13. 13.
    Gaucher A, Bertrand A, Tonnel F, Hocquard C, Adolphe J, Pere P (1985) Bone angioscintigraphy. Rev Rhum Mal Osteoartic 52:701–705PubMedGoogle Scholar
  14. 14.
    Wasser K, Moehler T, Nosas-Garcia S et al (2005) Correlation of MRI and histopathology of bone marrow in patients with multiple myeloma. Fortschr. Röntgenstr. 177:1116–1122CrossRefGoogle Scholar
  15. 15.
    Wasser K, Moehler T, Neben K et al (2004) Dynamic MRI of the bone marrow for monitoring multiple myeloma during treatment with thalidomide as monotherapy or in combination with CED chemotherapy. Fortschr. Röntgenstr. 176:1285–1295CrossRefGoogle Scholar
  16. 16.
    Hawighorst H, Knapstein PG, Weikel W et al (1997) Angiogenesis of uterine cervical carcinoma: characterization by pharmacokinetic magnetic resonance parameters and histological microvessel density with correlation to lymphatic involvement. Cancer Res 57:4777–4786PubMedGoogle Scholar
  17. 17.
    Hawighorst H, Libicher M, Knopp MV, Moehler T, Kauffmann GW, Kaick G (1999) Evaluation of angiogenesis and perfusion of bone marrow lesions: role of semiquantitative and quantitative dynamic MRI. J Magn Reson Imaging 10:286–294PubMedCrossRefGoogle Scholar
  18. 18.
    Wasser K, Klein SK, Fink C et al (2003) Evaluation of neoadjuvant chemotherapeutic response of breast cancer using dynamic MRI with high temporal resolution. Eur Radiol 13:80–87PubMedGoogle Scholar
  19. 19.
    Hillengass J, Wasser K, Delorme S et al (2007) Lumbar bone marrow microcirculation measurements from dynamic contrast-enhanced magnetic resonance imaging is a predictor of event-free survival in progressive multiple myeloma. Clin Cancer Res 13:475–481PubMedCrossRefGoogle Scholar
  20. 20.
    Brix G, Kiessling F, Lucht R et al (2004) Microcirculation and microvasculature in breast tumors: pharmacokinetic analysis of dynamic MR image series. Magn Reson Med 52:420–429PubMedCrossRefGoogle Scholar
  21. 21.
    Moehler TM, Hawighorst H, Neben K et al (2001) Bone marrow microcirculation analysis in multiple myeloma by contrast-enhanced dynamic magnetic resonance imaging. Int J Cancer 93:862–868PubMedCrossRefGoogle Scholar
  22. 22.
    Nosas-Garcia S, Moehler T, Wasser K et al (2005) Dynamic contrast-enhanced MRI for assessing the disease activity of multiple myeloma: a comparative study with histology and clinical markers. J Magn Reson Imaging 22:154–162PubMedCrossRefGoogle Scholar
  23. 23.
    Hoffmann U, Brix G, Knopp MV, Hess T, Lorenz WJ (1995) Pharmacokinetic mapping of the breast: a new method for dynamic MR mammography. Magn Reson Med 33:506–514PubMedCrossRefGoogle Scholar
  24. 24.
    Brix G, Schreiber W, Hoffmann U, Guckel F, Hawighorst H, Knopp MV (1997) Methodological approaches to quantitative evaluation of microcirculation in tissues with dynamic magnetic resonance tomography. Radiologe 37:470–480PubMedCrossRefGoogle Scholar
  25. 25.
    Wittenberg K (2001) The blade of grass sign. Radiology 221:199–200PubMedCrossRefGoogle Scholar
  26. 26.
    Tarquini R, Perfetto F, Tarquini B (1998) Endothelin-1 and Paget’s bone disease: is there a link. Calcif Tissue Int 63:118–120PubMedCrossRefGoogle Scholar
  27. 27.
    Pirzer R, Tilly N, Sommer U et al (2005) Endothelin-1 levels in patients with Paget’s disease of bone. Exp Clin Endocrinol Diabetes 113:598–601PubMedCrossRefGoogle Scholar
  28. 28.
    Fournier P, Boissier S, Filleur S et al (2002) Bisphosphonates inhibit angiogenesis in vitro and testosterone-stimulated vascular regrowth in the ventral prostate in castrated rats. Cancer Res 62:6538–6544PubMedGoogle Scholar

Copyright information

© European Society of Radiology 2007

Authors and Affiliations

  • M. Libicher
    • 1
    • 5
    Email author
  • C. Kasperk
    • 2
  • M. Daniels
    • 3
  • W. Hosch
    • 3
  • H.-U. Kauczor
    • 4
  • S. Delorme
    • 4
  1. 1.Department of RadiologyUniversity of CologneCologneGermany
  2. 2.Department of Medicine, Division of OsteologyUniversity of HeidelbergHeidelbergGermany
  3. 3.Department of RadiologyUniversity of HeidelbergHeidelbergGermany
  4. 4.Department of RadiologyGerman Cancer Research CenterHeidelbergGermany
  5. 5.Radiologische KlinikKlinikum der Universität zu KölnKölnGermany

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