Chronic hypercortisolism is associated with dramatic increase in fragility fractures. The evaluation of skeletal fragility in Cushings syndrome (CS) is a clinical challenge, since fractures may occur even in presence of normal bone mineral density (BMD). Recently, measurement of bone marrow fat (BMF) by vertebral magnetic resonance spectroscopy (MRS) was proposed as alternative tool for evaluating skeletal fragility in primary and secondary osteoporosis. Noteworthy, recent evidence shows that cortisol excess may cause BMF increase but it is still unknown whether it may be a biomarker of fracture risk in CS patients. In this cross-sectional study, we evaluated association between BMF and vertebral fractures (VFs) in 20 patients (5 M, age 44±13 years) with active CS (16 cases with ACTH-dependent and 4 with ACTH-independent CS). Fifteen healthy volunteers (4 M, age 43±12 years) acted as control group (CG) for BMF evaluation. BMF was measured by a single-voxel MRS (1,5 Tesla) on lumbar vertebral bodies, whereas VFs were assessed by a radiological and morphometric approach on thoracic and lumbar spine X-ray images. CS patients were also evaluated for lumbar spine BMD by dual-energy X-ray absorptiometry (DXA). Fractured vertebrae were excluded from BMF and BMD evaluations. Baseline parameters of pituitary-adrenal function and bone metabolism were also measured in CS patients. Overall, vertebral BMF was higher in CS patients than in CG (51.1+22.6% vs. 28.4+17.0%, P=0.003), and directly correlated with patients age at CS diagnosis (rho: 0.48; P=0.03), 24-hrs urine cortisol values (rho: 0.476; P=0.03), midnight serum cortisol values (rho 0.50; P=0.02), serum CTX (rho: 0.54; P=0.01), serum alkaline phosphatase (rho: 0.57; P=0.009) and urinary phosphate values (rho: 0.51; P=0.01). VFs were found in 13 CS patients (65%; 3 with normal BMD, 4 with osteopenia and 6 with either osteoporosis or low BMD for age, according to WHO criteria). Patients with VFs showed higher BMF than patients without (59.4 vs 35.8%, 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 (60.8+18.0 vs 57.7+21.5%; P=0.71). When the analysis was restricted to patients with normal BMD or osteopenia, VFs were still associated with higher BMF (60.8±18.1 vs. 35.8±21.8, P=0.05). This preliminary study provides a first evidence that vertebral adiposity is a marker of hypercortisolism-induced skeletal fragility and measurement of lumbar spine BMF by MRS may be a reliable tool for predicting VFs in endogenous CS.
18 - 21 May 2019
European Society of Endocrinology