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

• Published in: PloS one Vol. 14; no. 10; p. e0223432
• Main Authors: Batista, Sérgio Luchini, de Araújo, Iana Mizumukai, Carvalho, Adriana Lelis, Alencar, Maria Augusta V. S. D., Nahas, Andressa K., Elias, Jorge, Nogueira-Barbosa, Marcello H., Salmon, Carlos E. G., Elias, Paula C. L., Moreira, Ayrton C., Castro, Margaret, de Paula, Francisco J. A.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 15.10.2019; Public Library of Science (PLoS)
• Subjects: Absorptiometry; Adiponectin - metabolism; Adipose tissue; Adipose Tissue - pathology; Adrenocorticotropic hormone; Adult; Biochemistry; Biology and Life Sciences; Biomedical materials; Body Weight; Bone and Bones - pathology; Bone Density; Bone marrow; Bone Marrow - pathology; Bone mineral density; Cancellous bone; Cancellous Bone - pathology; Clinical medicine; Complications and side effects; Cooperation; Cushing syndrome; Cushing's disease; Diabetes; Diagnosis; Diagnostic imaging; Disease control; Dual energy X-ray absorptiometry; Endocrinology; Fractures; Glucose; Health aspects; Humans; Insulin; Insulin Resistance; Leptin - metabolism; Levels; Linear Models; Lipids; Lipids - analysis; Magnetic resonance; Magnetic resonance imaging; Medical research; Medical schools; Medicine; Medicine and Health Sciences; Metabolic disorders; Metabolic syndrome; Metabolic Syndrome - complications; Metabolism; Nervous system diseases; Obesity; Osteocalcin; Osteoporosis; Patient outcomes; Physiological aspects; Pituitary; Pituitary ACTH Hypersecretion - complications; Quality; Serum levels; Spine; Spine (lumbar); Type 2 diabetes; Womens health; Brazil; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0223432

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.