Beyond the metabolic syndrome: Visceral and marrow adipose tissues impair bone quantity and quality in Cushing’s disease

Abstract

The present study was designed to evaluate the relationship between bone traits [bone mineral density (BMD) and trabecular bone score (TBS)] and the accumulation of fat in adipose tissues [abdominal subcutaneous (SAT), visceral (VAT), marrow (MAT) and intrahepatic lipids (IHL)], as well as insulin resistance, in subjects with Cushing’s disease (CD). The study included control (C = 27), paired (P = 16) and Cushing’s disease (CD = 10) groups, which underwent biochemical assessment, dual X-ray absorptiometry, TBS, and magnetic resonance imaging to determine fat deposits. The CD group showed higher serum levels of glucose and insulin, as well as HOMA-IR values, but lower circulatory levels of osteocalcin, in comparison to C and P. The CD group exhibited lower L1-L4 BMD than P (P = 1.059 ± 0.141 vs CD = 0.935 ± 0.093 g/cm2, p < 0.05) (Fig 1A). The lumbar spine BMD from the C group was similar to the other groups. TBS was lower in CD than in P and C (C = 1.512±0.077 vs P = 1.405±0.150 vs CD = 1.135±0.136; p<0.05); there was also significant difference between C and P (p<0.05). MAT, VAT, and IHL were higher in CD than in C and P (p<0.05). Considering all subjects, there was a positive association between TBS with both lumbar spine BMD (R2 = 0.45; p<0.0001) and osteocalcin (R2 = 0.44; p = 0.05). TBS was negatively associated with MAT (R2 = 0.49; p = 0.01), VAT (R2 = 0.55; p<0.05), and HOMA-IR (R2 = 0.44; p<0.01). MAT was positively related with VAT (R2 = 0.44; p<0.01) and IHL (R2 = 0.41; p<0.05). In CD, insulin resistance and adipose tissue dysfunction, including high MAT, are active players in bone deterioration, as confirmed by lower lumbar spine BMD and lower TBS. Thus, our findings point to an additional component of the already well-known complex mechanisms of osteoporosis associated with hypercortisolism.

DXA parameters, Trabecular Bone Score (TBS) and Bone Mineral Density (BMD), in fracture risk prediction in endocrine-mediated secondary osteoporosis

“…It has been shown that hypercortisolism has a negative effect on bone due to decreased bone formation that it causes. Nevertheless, only a mild decline in BMD has been reported; whereas the TBS decline was more pronounced [ 87 , 88 ]. Moreover, TBS was lower in CD than in primary obesity patients, indicating the sensitivity of TBS to detect the variations along the hypercortisolism spectrum.…”

Update on trabecular bone score

“…In general, compared to control subjects, TBS was reported to be lower in patients with diabetes ( 42 , 57 – 59 ), primary hyperparathyroidism ( 60 – 64 ), acromegaly ( 65 – 68 ), anorexia nervosa ( 69 , 70 ), hypercortisolism ( 71 – 73 ), primary aldosteronism (especially in women) ( 74 ), with prolonged GC exposure ( 75 – 84 ), rheumatoid arthritis and rheumatic disease ( 85 – 87 ), aromatase inhibition ( 88 ), kidney transplant recipients ( 89 ), as well as in patients on hemodialysis ( 90 , 91 ). In differentiated thyroid carcinomas, TBS was found to be lower in patients receiving long-term suppressive doses of thyroid-stimulating hormone than in patients receiving shorter-term therapy ( 92 – 94 ).…”

The Severity of Bone Loss: A Comparison Between Cushing’s Disease and Cushing’s Syndrome

“…The structural and functional skeletal damage is disabling and correlates with the patients' reported low quality of life [3,4]. According to data on bone density in endogenous hypercortisolism, patients with CS of adrenal, pituitary, or ectopic origin have marked osteopenia/osteoporosis [5,6].…”