Vertebral bone marrow fat fraction changes in postmenopausal women with breast cancer receiving combined aromatase inhibitor and bisphosphonate therapy

BMC Musculoskelet Disord. 2019 Nov 6;20(1):515. doi: 10.1186/s12891-019-2916-2.


Background: Quantification of vertebral bone marrow (VBM) water-fat composition has been proposed as advanced imaging biomarker for osteoporosis. Estrogen deficiency is the primary reason for trabecular bone loss in postmenopausal women. By reducing estrogen levels aromatase inhibitors (AI) as part of breast cancer therapy promote bone loss. Bisphosphonates (BP) are recommended to counteract this adverse drug effect. The purpose of our study was to quantify VBM proton density fat fraction (PDFF) changes at the lumbar spine using chemical shift encoding-based water-fat MRI (CSE-MRI) and bone mineral density (BMD) changes using dual energy X-ray absorptiometry (DXA) related to AI and BP treatment over a 12-month period.

Methods: Twenty seven postmenopausal breast cancer patients receiving AI therapy were recruited for this study. 22 subjects completed the 12-month study. 14 subjects received AI and BP (AI+BP), 8 subjects received AI without BP (AI-BP). All subjects underwent 3 T MRI. An eight-echo 3D spoiled gradient-echo sequence was used for CSE-based water-fat separation at the lumbar spine to generate PDFF maps. After manual segmentation of the vertebral bodies L1-L5 PDFF values were extracted for each vertebra and averaged for each subject. All subjects underwent DXA of the lumbar spine measuring the average BMD of L1-L4.

Results: Baseline age, PDFF and BMD showed no significant difference between the two groups (p > 0.05). There was a relative longitudinal increase in mean PDFF (∆relPDFF) in both groups (AI+BP: 5.93%; AI-BP: 3.11%) which was only significant (p = 0.006) in the AI+BP group. ∆relPDFF showed no significant difference between the two groups (p > 0.05). There was no significant longitudinal change in BMD (p > 0.05).

Conclusions: Over a 12-month period, VBM PDFF assessed with CSE-MRI significantly increased in subjects receiving AI and BP. The present results contradict previous results regarding the effect of only BP therapy on bone marrow fat content quantified by magnetic resonance spectroscopy and bone biopsies. Future longer-term follow-up studies are needed to further characterize the effects of combined AI and BP therapy.

Keywords: Aromatase inhibitor; Bisphosphonates; Osteoporosis; Proton density fat fraction; Vertebral bone marrow.

Publication types

  • Observational Study

MeSH terms

  • Absorptiometry, Photon
  • Adipose Tissue / diagnostic imaging*
  • Adipose Tissue / drug effects
  • Adipose Tissue / pathology
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Aromatase Inhibitors / adverse effects*
  • Bone Density / drug effects
  • Bone Density Conservation Agents / administration & dosage
  • Bone Marrow / diagnostic imaging*
  • Bone Marrow / drug effects
  • Bone Marrow / pathology
  • Breast Neoplasms / drug therapy*
  • Cancellous Bone / diagnostic imaging
  • Cancellous Bone / drug effects
  • Cancellous Bone / pathology
  • Female
  • Follow-Up Studies
  • Humans
  • Imaging, Three-Dimensional
  • Lumbar Vertebrae / diagnostic imaging
  • Lumbar Vertebrae / drug effects
  • Lumbar Vertebrae / pathology
  • Magnetic Resonance Imaging
  • Middle Aged
  • Osteoporosis / chemically induced
  • Osteoporosis / diagnostic imaging*
  • Osteoporosis / physiopathology
  • Osteoporosis / prevention & control
  • Postmenopause / physiology
  • Zoledronic Acid / administration & dosage


  • Aromatase Inhibitors
  • Bone Density Conservation Agents
  • Zoledronic Acid