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High bone marrow fat in patients with Cushing’s syndrome and vertebral fractures

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Abstract

Purpose

The evaluation of skeletal fragility in Cushing’s syndrome (CS) is a clinical challenge, since dual-energy X-ray absorptiometry (DXA) does not capture abnormalities in bone microstructure induced by glucocorticoid excess. Hypercortisolism was shown to increase bone marrow adiposity, but it is still unknown whether high bone marrow fat (BMF) as measured by vertebral magnetic resonance spectroscopy may predict fracture risk in this clinical setting. In this cross-sectional study, we evaluated the association between BMF and vertebral fractures (VFs) in patients with CS.

Methods

Twenty patients (5 M, age 44 ± 13 years) with active CS were evaluated for morphometric VFs, lumbar spine BMF, and bone mineral density (BMD). Fifteen healthy volunteers (4 M, age 43 ± 12 years) acted as control group for BMF evaluation.

Results

BMF was significantly higher in CS patients vs. controls (52.0% vs. 27.0%, p < 0.01), and was directly correlated with patients’ age (p = 0.03), 24-hours urine-free cortisol (p = 0.03), midnight serum cortisol (p = 0.02), and serum CTX (p = 0.01). Patients with VFs (13 cases) showed significantly higher BMF vs. patients without VFs (65.0% vs. 24.0%, p = 0.03). Fractured patients with either normal BMD or osteopenia showed comparable BMF to fractured patients with either osteoporosis or low BMD for age (p = 0.71). When the analysis was restricted to patients with normal BMD or osteopenia, VFs were still significantly associated with higher BMF (p = 0.05).

Conclusions

This study provides a first evidence that vertebral adiposity may be a marker of hypercortisolism-induced skeletal fragility and measurement of spine BMF could have a role in the diagnostic work-up for the assessment of fracture risk in CS.

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Funding

This work was funded by a grant of the Ministry of Education, University and Research of the Italian Government (PRIN 2015 - Grant number 2015ZHKFTA).

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  1. These authors contributed equally: F. Ferraù, S. Giovinazzo

Authors and Affiliations

  1. Endocrine Unit, University Hospital “AOU Policlinico G. Martino”, Messina, Italy

    Francesco Ferraù, Salvatore Giovinazzo, Erika Messina & Salvatore Cannavò

  2. Department of Human Pathology of Adulthood and Childhood “G. Barresi”, University of Messina, Messina, Italy

    Francesco Ferraù & Salvatore Cannavò

  3. Neuroradiological Unit of University Hospital “AOU Policlinico G. Martino”, Messina, Italy

    Agostino Tessitore, Sergio Vinci & Francesca Granata

  4. Department of Biomedical Sciences and Morphological and Functional Imaging of University of Messina, Messina, Italy

    Sergio Vinci & Francesca Granata

  5. Department of Biomedical Sciences, Humanitas University, Rozzano (MI), Italy

    Gherardo Mazziotti & Andrea Lania

  6. Endocrine Unit, Humanitas Clinical and Research Center, Rozzano (MI), Italy

    Gherardo Mazziotti & Andrea Lania

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  1. Francesco Ferraù
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G.M. received consultant fees by Ipsen and Novartis; A.L. received grants from Ipsen, Pfizer, Novartis and speaker honoraria from Ipsen and Pfizer; S.C. served in medical advisory boards of HRA. The remaining authors declare that they have no conflict of interest.

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Ferraù, F., Giovinazzo, S., Messina, E. et al. High bone marrow fat in patients with Cushing’s syndrome and vertebral fractures. Endocrine 67, 172–179 (2020). https://doi.org/10.1007/s12020-019-02034-4

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