Annals of Nuclear Medicine

, Volume 27, Issue 9, pp 802–807 | Cite as

Bone scintigraphy as a new imaging biomarker: the relationship between bone scan index and bone metabolic markers in prostate cancer patients with bone metastases

  • Hiroshi WakabayashiEmail author
  • Kenichi Nakajima
  • Atsushi Mizokami
  • Mikio Namiki
  • Anri Inaki
  • Junichi Taki
  • Seigo Kinuya
Original Article



A computer-aided diagnosis system for bone scintigraphy with a semiquantitative index from the Bone Scan Index (BSI) has been used to quantify the spread of bone metastases. However, few papers have made clear associations among BSI, bone metabolic markers, and prostate-specific antigen (PSA). This retrospective study aimed to examine these relationships in prostate cancer patients with bone metastases.


A total of 158 scans from 52 patients (number of median examinations/person 3, range 1–8; median age 71 years, age range 46–86) were included. The intervals between bone scans and blood examinations were 0–16 days (median 0 day). The serum markers of PSA, pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (1-CTP), bone alkaline phosphatase (BAP), and tartrate-resistant acid phosphatase-5b (TRACP-5b) were examined. Subjects were divided into 4 groups according to BSI; Group A: 0 to <2, Group B: 2 to <4, Group C: 4 to <8, and Group D: over 8. BSI, which corresponded to the amount of metastatic lesion, was automatically calculated by BONENAVI® software (FUJIFILM RI Pharma, Co. Ltd., Tokyo, Japan; Exini Bone, Exini Diagnostics, Sweden).


All bone scans showed high uptake with bone metastases. BSI was correlated significantly with the serum 1-CTP, serum BAP, serum TRACP-5b, logBAP, logTRACP-5b, and logPSA (r = 0.39, 0.66, 0.69, 0.71, 0.62 and 0.41, respectively). BSI did not correlate significantly with the serum PSA. The statistical F value was 11 in the serum 1-CTP, 31 in serum BAP, 29 in logBAP, 19 in serum TRACP-5b, 14 in logTRACP-5b, 3 in serum PSA, and 9 in logPSA by analysis of variance. Comparison by Dunnett’s test showed significantly higher values in Group D for all original bone metabolic markers and the logPSA, Group C for the serum BAP, logBAP, serum TRACP-5b, and logTRACP-5b, and Group B for the logTRACP-5b compared with Group A.


The changes in BSI showed a close relationship with all bone metabolic markers but not with the serum PSA. The BSI is confirmed to reflect the activity and extent of bone metastases, and can be used as an imaging biomarker.


Bone scan index Bone metastases Prostate-specific antigen Bone metabolic marker 


Conflict of interest



  1. 1.
    Bubendorf L, Schöpfer A, Wagner U, Sauter G, Moch H, Willi N, et al. Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients. Hum Pathol. 2000;31:578–83.CrossRefPubMedGoogle Scholar
  2. 2.
    Janckila AJ, Takahashi K, Sun SZ, Yam LT. Tartrate-resistant acid phosphatase isoform 5b as serum marker for osteoclastic activity. Clin Chem. 2001;47:74–80.PubMedGoogle Scholar
  3. 3.
    Risteli J, Elomaa I, Niemi S, Novamo A, Risteli L. Radioimmunoassay for the pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen: a new serum marker of bone collagen degradation. Clin Chem. 1993;39:635–40.PubMedGoogle Scholar
  4. 4.
    Lein M, Wirth M, Miller K, Eickenberg HU, Weissbach L, Schmidt K, et al. Serial markers of bone turnover in men with metastatic prostate cancer treated with zoledronic acid for detection of bone metastases progression. Eur Urol. 2007;52:1381–7.CrossRefPubMedGoogle Scholar
  5. 5.
    Izumi K, Mizokami A, Itai S, Shima T, Shigehara K, Miwa S, et al. Increases in bone turnover marker levels at an early phase after starting zoledronic acid predicts skeletal-related events in patients with prostate cancer with bone metastasis. BJU Int. 2012;109:394–400.CrossRefPubMedGoogle Scholar
  6. 6.
    Soloway MS, Hardeman SW, Hickey D, Raymond J, Todd B, Soloway S, et al. Stratification of patients with metastatic prostate cancer based on extent of disease on initial bone scan. Cancer. 1988;61:195–202.CrossRefPubMedGoogle Scholar
  7. 7.
    Zafeirakis AG, Papatheodorou GA, Limouris GS. Clinical and imaging correlations of bone turnover markers in prostate cancer patients with bone only metastases. Nucl Med Commun. 2010;31:249–53.CrossRefPubMedGoogle Scholar
  8. 8.
    Horikoshi H, Kikuchi A, Onoguchi M, Sjöstrand K, Edenbrandt L. Computer-aided diagnosis system for bone scintigrams from Japanese patients: importance of training database. Ann Nucl Med. 2012;26:622–6.CrossRefPubMedGoogle Scholar
  9. 9.
    Brown JE, Cook RJ, Major P, Lipton A, Saad F, Smith M, et al. Bone turnover markers as predictors of skeletal complications in prostate cancer, lung cancer, and other solid tumors. J Natl Cancer Inst. 2005;97:59–69.CrossRefPubMedGoogle Scholar
  10. 10.
    Lipton A, Cook R, Saad F, Major P, Garnero P, Terpos E, et al. Normalization of bone markers is associated with improved survival in patients with bone metastases from solid tumors and elevated bone resorption receiving zoledronic acid. Cancer. 2008;113:193–201.CrossRefPubMedGoogle Scholar
  11. 11.
    Fontana A, Delmas PD. Markers of bone turnover in bone metastases. Cancer. 2000;88:2952–60.CrossRefPubMedGoogle Scholar
  12. 12.
    Tsai SH, Chen CY, Ku CH, Janckila AJ, Yam LT, Yu JC, et al. The semiquantitative bone scintigraphy index correlates with serum tartrate-resistant acid phosphatase activity in breast cancer patients with bone metastasis. Mayo Clin Proc. 2007;82:917–26.CrossRefPubMedGoogle Scholar
  13. 13.
    Ozu C, Nakashima J, Horiguchi Y, Oya M, Ohigashi T, Murai M. Prediction of bone metastases by combination of tartrate-resistant acid phosphatase, alkaline phosphatase and prostate specific antigen in patients with prostate cancer. Int J Urol. 2008;15:419–22.CrossRefPubMedGoogle Scholar
  14. 14.
    Keller Evan T, Brown Julie. Prostate cancer bone metastases promote both osteolytic and osteoblastic activity. J Cell Biochem. 2004;91:718–29.CrossRefPubMedGoogle Scholar
  15. 15.
    Ulmert D, Kaboteh R, Fox JJ, Savage C, Evans MJ, Lilja H, et al. A novel automated platform for quantifying the extent of skeletal tumour involvement in prostate cancer patients using the Bone Scan Index. Eur Urol. 2012;62:78–84.CrossRefPubMedGoogle Scholar
  16. 16.
    Dennis ER, Jia X, Mezheritskiy IS, Stephenson RD, Schoder H, Fox JJ, et al. Bone Scan Index: a quantitative treatment response biomarker for castration-resistant metastatic prostate cancer. J Clin Oncol. 2012;30:519–24.CrossRefPubMedGoogle Scholar
  17. 17.
    Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.CrossRefPubMedGoogle Scholar
  18. 18.
    Sadik M, Suurkula M, Höglund P, Järund A, Edenbrandt L. Quality of planar whole-body bone scan interpretations—a nationwide survey. Eur J Nucl Med Mol Imaging. 2008;35:1464–72.CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society of Nuclear Medicine 2013

Authors and Affiliations

  • Hiroshi Wakabayashi
    • 1
    Email author
  • Kenichi Nakajima
    • 1
  • Atsushi Mizokami
    • 2
  • Mikio Namiki
    • 2
  • Anri Inaki
    • 1
  • Junichi Taki
    • 1
  • Seigo Kinuya
    • 1
  1. 1.Department of Nuclear MedicineKanazawa University HospitalKanazawaJapan
  2. 2.Department of Integrative Cancer Therapy and Urology, Division of Cancer MedicineGraduate School of Medical Science, Kanazawa UniversityKanazawaJapan

Personalised recommendations