European Radiology

, Volume 27, Issue 3, pp 995–1003 | Cite as

Spinal multiparametric MRI and DEXA changes over time in men with prostate cancer treated with androgen deprivation therapy: a potential imaging biomarker of treatment toxicity

  • Jarad MartinEmail author
  • Jameen Arm
  • Joanne Smart
  • Kerrin Palazzi
  • Anne Capp
  • Paul Ainsworth
  • Gary Cowin
Magnetic Resonance



To explore changes in bone mineral density (BMD) measured by DEXA and MRS fat fraction (FF), Dixon FF, and ADC in lower spinal vertebral bodies in men with prostate cancer treated with androgen deprivation therapy (ADT).


Twenty-eight men were enrolled onto a clinical trial. All received ADT. DEXA imaging was performed at baseline and 12 months. L-spine MRI was done at baseline and 6 months.


The number of patients who underwent DEXA, Dixon, ADC, and MRS at baseline/follow-up were 28/27, 28/26, 28/26, and 22/20. An increase in FF was observed from T11 to S2 (average 1 %/vertebra). There was a positive correlation between baseline MRS FF and Dixon FF (r = 0.85, p < 0.0001) and a negative correlation between MRS FF and ADC (r = -0.56, p = 0.036). Over 6 months, MRS FF increased by a median of 25 % in relative values (p = 0.0003), Dixon FF increased (p < 0.0001) and ADC values decreased (p = 0.0014). Men with >5 % BMD loss after 1 year had triple the percentage increase in MRS FF at 6 months (61.1 % vs. 20.9 %, p = 0.19).


Changes are observed on L-spine MRI after 6 months of ADT. Further investigation is warranted of MRS change as a potential predictive biomarker for later BMD loss.

Key Points

Spinal marrow fat fraction increases after 6 months of androgen deprivation therapy.

More inferior vertebral bodies tend to have higher fat fractions.

MRS fat fraction changes were associated with later changes in DEXA BMD.


Magnetic resonance imagining Bone density Prostate neoplasms Biomarkers Toxicity 



Androgen depravation therapy


Bone mineral density


Dual-energy X-ray absorptiometry


Diffusion weighted imaging


Fat fraction


High risk prostate cancer


Point resolved spectroscopy


Prostate cancer imaging, treatment, and toxicity


Single voxel spectroscopic



The authors wish to acknowledge the assistance of Katie Baker and Hannah Woodford who assisted in MRI data extraction. Mary-Clare Hanlon assisted with manuscript submission. Peter Stanwell assisted with MRI sequence programming. Abbvie pharmaceuticals provided an unrestricted investigator initiated grant which funded the scans, trial management and statistical analysis. All analysis and manuscript preparation was performed without any input from Abbvie Pharmaceuticals.

The scientific guarantor of this publication is Associate Professor Jarad Martin. The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. This study has received funding by Abbvie Pharmaceuticals. Dr Kerrin Palazzi (one of the authors) kindly provided statistical advice for this manuscript. Institutional Review Board approval was obtained. Written informed consent was obtained from all subjects (patients) in this study.

Some of the same subjects also had assays performed for circulating tumour cells, as well as a nomogram guided radiotherapy target volume, both of which have been reported separately. The current study completely addresses bone health and imaging, neither of which have been reported in the previous manuscripts.

Methodology: Prospective, diagnostic or prognostic study / observational / experimental, performed at one institution.


  1. 1.
    D'Amico AV, Cote K, Loffredo M, Renshaw AA, Schultz D (2002) Determinants of prostate cancer-specific survival after radiation therapy for patients with clinically localized prostate cancer. J Clin Oncol Off J Am Soc Clin Oncol 20:4567–4573CrossRefGoogle Scholar
  2. 2.
    Bolla M, Van Tienhoven G, Warde P et al (2010) External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomised study. Lancet Oncol 11:1066–1073CrossRefPubMedGoogle Scholar
  3. 3.
    Mason MD, Parulekar WR, Sydes MR et al (2015) Final report of the intergroup randomized study of combined androgen-deprivation therapy plus radiotherapy versus androgen-deprivation therapy alone in locally advanced prostate cancer. J Clin Oncol Off J Am Soc Clin Oncol 33:2143–2150CrossRefGoogle Scholar
  4. 4.
    Shahinian VB, Kuo YF, Freeman JL, Goodwin JS (2005) Risk of fracture after androgen deprivation for prostate cancer. N Engl J Med 352:154–164CrossRefPubMedGoogle Scholar
  5. 5.
    Oefelein MG, Ricchiuti V, Conrad W, Resnick MI (2002) Skeletal fractures negatively correlate with overall survival in men with prostate cancer. J Urol 168:1005–1007CrossRefPubMedGoogle Scholar
  6. 6.
    Higano CS (2008) Androgen-deprivation-therapy-induced fractures in men with nonmetastatic prostate cancer: what do we really know? Nat Clin Pract Urol 5:24–34CrossRefPubMedGoogle Scholar
  7. 7.
    Grossmann M, Hamilton EJ, Gilfillan C, Bolton D, Joon DL, Zajac JD (2011) Bone and metabolic health in patients with non-metastatic prostate cancer who are receiving androgen deprivation therapy. Med J Aust 194:301–306PubMedGoogle Scholar
  8. 8.
    Alibhai SM, Yun L, Cheung AM, Paszat L (2012) Screening for osteoporosis in men receiving androgen deprivation therapy. JAMA 307:255–256CrossRefPubMedGoogle Scholar
  9. 9.
    Smith MR, McGovern FJ, Zietman AL et al (2001) Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer. N Engl J Med 345:948–955CrossRefPubMedGoogle Scholar
  10. 10.
    Paccou J, Hardouin P, Cotten A, Penel G, Cortet B (2015) The role of bone marrow fat in skeletal health: usefulness and perspectives for clinicians. J Clin Endocrinol Metab 100:3613–3621CrossRefPubMedGoogle Scholar
  11. 11.
    Rosen CJ, Bouxsein ML (2006) Mechanisms of disease: is osteoporosis the obesity of bone? Nat Clin Pract Rheumatol 2:35–43CrossRefPubMedGoogle Scholar
  12. 12.
    Blake GM, Fogelman I (2010) An update on dual-energy X-ray absorptiometry. Semin Nucl Med 40:62–73CrossRefPubMedGoogle Scholar
  13. 13.
    Wu R, Woodford H, Capp A et al (2015) A prospective study of nomogram-based adaptation of prostate radiotherapy target volumes. Radiat Oncol 10:1–9CrossRefGoogle Scholar
  14. 14.
    Greenspan SL, Nelson JB, Trump DL et al (2008) Skeletal health after continuation, withdrawal, or delay of alendronate in men with prostate cancer undergoing androgen-deprivation therapy. J Clin Oncol Off J Am Soc Clin Oncol 26:4426–4434CrossRefGoogle Scholar
  15. 15.
    Barentsz JO, Weinreb JC, Verma S et al (2016) Synopsis of the PI-RADS v2 guidelines for multiparametric prostate magnetic resonance imaging and recommendations for use. Eur Urol 69:41–49CrossRefPubMedGoogle Scholar
  16. 16.
    Greenspan SL (2005) Bone loss after initiation of androgen deprivation therapy in patients with prostate cancer. J Clin Endocrinol Metab 90:6410–6417CrossRefPubMedGoogle Scholar
  17. 17.
    Ueda Y, Miyati T, Ohno N et al (2010) Apparent diffusion coefficient and fractional anisotropy in the vertebral bone marrow. J Magn Reson Imaging JMRI 31:632–635CrossRefPubMedGoogle Scholar
  18. 18.
    Martin J, Nicholson G, Cowin G, Ilente C, Wong W, Kennedy D (2014) Rapid determination of vertebral fat fraction over a large range of vertebral bodies. J Med Imaging Radiat Oncol 58:155–163CrossRefPubMedGoogle Scholar
  19. 19.
    Bolan PJ, Arentsen L, Sueblinvong T et al (2013) Water-fat MRI for assessing changes in bone marrow composition due to radiation and chemotherapy in gynecologic cancer patients. J Magn Reson Imaging JMRI 38:1578–1584CrossRefPubMedGoogle Scholar
  20. 20.
    Carmona R, Pritz J, Bydder M et al (2014) Fat composition changes in bone marrow during chemotherapy and radiation therapy. Int J Radiat Oncol Biol Phys 90:155–163CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Liney GP, Bernard CP, Manton DJ, Turnbull LW, Langton CM (2007) Age, gender, and skeletal variation in bone marrow composition: a preliminary study at 3.0 Tesla. J Magn Reson Imaging JMRI 26:787–793CrossRefPubMedGoogle Scholar
  22. 22.
    Shen W, Chen J, Gantz M et al (2012) MRI-measured pelvic bone marrow adipose tissue is inversely related to DXA-measured bone mineral in younger and older adults. Eur J Clin Nutr 66:983–988CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Hotker AM, Garcia-Aguilar J, Gollub MJ (2014) Multiparametric MRI of rectal cancer in the assessment of response to therapy: a systematic review. Dis Colon Rectum 57:790–799CrossRefPubMedGoogle Scholar
  24. 24.
    Kim S, Loevner L, Quon H et al (2009) Diffusion-weighted magnetic resonance imaging for predicting and detecting early response to chemoradiation therapy of squamous cell carcinomas of the head and neck. Clin Cancer Res Off J Am Assoc Cancer Res 15:986–994CrossRefGoogle Scholar
  25. 25.
    Hotker AM, Mazaheri Y, Zheng J et al (2015) Prostate cancer: assessing the effects of androgen-deprivation therapy using quantitative diffusion-weighted and dynamic contrast-enhanced MRI. Eur Radiol 25:2665–2672CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Jones M, Hruby G, Stanwell P et al (2015) Multiparametric MRI as an outcome predictor for anal canal cancer managed with chemoradiotherapy. BMC Cancer 15:281CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© European Society of Radiology 2016

Authors and Affiliations

  • Jarad Martin
    • 1
    • 2
    • 3
    Email author
  • Jameen Arm
    • 4
  • Joanne Smart
    • 1
  • Kerrin Palazzi
    • 5
  • Anne Capp
    • 1
    • 2
  • Paul Ainsworth
    • 6
  • Gary Cowin
    • 3
  1. 1.Department of Radiation OncologyCalvary Mater NewcastleNewcastleAustralia
  2. 2.School of Medicine and Public HealthUniversity of NewcastleNewcastleAustralia
  3. 3.Centre for Advanced ImagingUniversity of QueenslandBrisbaneAustralia
  4. 4.Hunter New England ImagingNewcastleAustralia
  5. 5.CREDITSS, Hunter Medical Research InstituteNewcastleAustralia
  6. 6.Department of UrologyHunter New England HealthNewcastleAustralia

Personalised recommendations