For patients with endogenous glucocorticoid excess, bone and vascular diseases may co-occur often, and arterial stiffness in these patients may be related to weakened bone quality rather than bone loss, according to findings published in Bone Reports.

The findings indicate that “glucocorticoid excess may perturb the bone-vascular access,” according to the researchers.

“Since endogenous [Cushing’s Syndrome (CS)] occurs rarely, much of our knowledge about glucocorticoid-induced osteoporosis and atherosclerosis have been from studies of patients treated with exogenous glucocorticoids,” Maki Yokomoto-Umakoshi, MD, and colleagues wrote. “These studies are limited by the fact that patients treated with glucocorticoids usually have primary disease(s) that may affect bone and vascular conditions. In this regard, endogenous CS would provide a better understanding of the direct effect of glucocorticoid excess on bone and vascular pathologies.”

Dr. Yokomoto-Umakoshi and colleagues sought to examine the role of endogenous glucocorticoid excess in the coexistence of bone and vascular diseases. The study included 194 patients with adrenal tumors (ATs), either autonomous cortisol secretion (ACS; N=97) or non-functional (N=97) ATs. The researchers further categorized ACS into overt CS (N=17) and subclinical CS (SCS; N=80). They defined arterial stiffness as a brachial-ankle pulse wave velocity (baPWV) of greater than or equal to 1,800 cm/s.

Extent of Cortisol Excess Influences Arterial Stiffness & Bone Outcomes

Patients with ACS had higher rates of coexisting vertebral fractures and arterial stiffness (23% vs 2%; P<0.001) and vertebral fractures and abdominal aortic calcification (22% vs 1%; P<0.001) than patients with non-functional ATs. Among patients with ACS, baPWV negatively correlated with trabecular bone score (TBS; P=0.002), but not with bone mineral density, and vertebral fracture was associated with arterial stiffness in the logistic regression analysis.

“In the multivariate analysis of variance, the degree of cortisol excess (defined as CS, SCS, and non-functional AT) determined the correlation between TBS and baPWV (partial η2=0.07; P<0.001),” the investigators wrote. “In the analysis of covariance, patients with coexisting vertebral fracture and arterial stiffness had higher levels of serum cortisol after the 1 mg dexamethasone suppression test than those without.”

The results may be partially explained by the concept that bone quality, rather than bone mass, underscores the pathology of glucocorticoid-induced osteoporosis, Dr. Yokomoto-Umakoshi and colleagues noted.

“Further studies are required to address whether or not oxidative stress, a major determinant of bone deterioration and atherosclerosis, mediates coexisting bone and vascular diseases in patients with endogenous glucocorticoid excess,” the study team wrote.