Volumetric BMD and bone strength estimates on QCT-based finite element analysis are impaired in patients with Cushing’s syndrome in long-term remission

MS. Batule Nallim*^a (Dr), E. Soudah^b (Dr), L. Martel-Duguech^c (Dr), J. Malouf Sierra^d (Dr), M. Puig-Domingo^e (Prof), S. Webb^c (Prof), E. Valassi^e (Prof)

^a Germans Trias i Pujol Hospital and Research Institute, Badalona, SPAIN ; ^b International Centre for Numerical Methods in Engineering (CIMNE), Barcelona, SPAIN ; ^c IIB-Sant Pau and Department of Endocrinology-Medicine, Hospital Sant Pau, Barcelona, SPAIN ; ^d Mineral Metabolism Unit, Hospital Sant Pau, Barcelona, SPAIN ; ^e Germans Trias i Pujol Hospital and Research Institute, Barcelona, SPAIN

* sol_batule@hotmail.com

Background

Cortisol excess in active Cushing’s syndrome (CS) is associated with bone loss and skeletal fragility. Although bone mineral density (BMD), as measured using dual-energy X-ray absorptiometry (DXA), may partly recover within few years after remission, fracture risk remains elevated. No studies have evaluated volumetric BMD and mechanical properties in patients with long-term remission thus far.

Patients and methods: Thirty-six women with CS in remission [median age (interquartile range), 51 (15); mean (±SD) BMI, 27±4 Kg/m²] and 36 age-, BMI- and menopausal status-matched female controls were included. Median time of remission was 13 years (8). Quantitative computed tomography (QCT) was used to assess volumetric bone mineral density (vBMD) at total hip (TH), femoral neck (FN), trochanter (TR) and intertrochanteric (IT) as well as mechanical properties (buckling ratio, cross sectional area and average cortical thickness) at FN. A finite element model was generated from QCT images to calculate tissue stiffness, principal stress and strain. A patient-specific sideways-fall impact was simulated using the patient mass and height. Areal BMD (aBMD) at lumbar spine and hip was assessed by DXA.

Results

Trabecular vBMD was lower in CS as compared with controls at all the femoral sites analyzed except TH, and cortical vBMD was lower in CS patients than controls at all the sites except the trochanter (p<0.05 for all comparisons). Cortical thickness was lower and buckling ratio was greater in CS as compared with controls, indicating more cortical elastic instability (p<0.01 for all comparisons) in the former. The finite element analysis showed that bone stiffness was lower while principal stress and strain were higher in CS patients as compared with controls, indicating a higher fracture risk (p<0.05 for all comparisons) in CS. DXA-derived measures were similar between patients and controls. After adjusting for menopause, diagnosis of CS was the main predictor of all the parameters examined, except trabecular vBMD at TH.

Conclusions

CS female patients in remission have reduced vBMD, and impaired mechanical properties and strength estimates regardless of the menopausal status. These abnormalities may contribute to persistently elevated fracture risk long-term after resolution of cortisol excess.

The author has declared no conflict of interest.