Zhanna E. Belaya
The National Research Center for Endocrinology, Moscow, Russia

Liudmila Y. Rozhinskaya
Alexander G. Solodovnikov
Natalia V. Dragunova
Galina A. Melnichenko

Series: Endocrinology Research and Clinical Developments
BISAC: MED027000

This work is primarily focused on data related to the characteristics, pathogenesis and treatment of bone complications in patients with endogenous Cushing’s syndrome of different etiology. The chapter is based on the retrospective and prospective data of patients with active Cushing’s syndrome as well as on literature review. Special attention is paid to discussing pregnancy and bisphosphonate use, outlining a clinical case of a successful pregnancy in a patient treated with ibandronic acid (Bonviva).

In order to evaluate the major predictors of low-traumatic fracture in patients with Cushing’s syndrome, the most fully available data on 223 consecutive patients with clinically evident active Cushing’s syndrome receiving treatment during 2001-2011 was analyzed in a single referral center. Among 223 patients with active Cushing’s syndrome, low traumatic fractures were confirmed in 43%; in most cases there were multiple fractures of the vertebras. Bone mineral density (BMD) loss was mild. Patients with fractures statistically significantly differed in terms of sex (men fractured more frequently than women), had lower osteocalcin (OC) and higher 24 hour urinary free cortisol (24hUFC) as well as late-night serum cortisol. After regression analysis, the main predictors of low-traumatic fracture occurrence was 24h UFC (p<0,001) and separately analyzed late-night serum cortisol (p<0,001). The severity of hypercortisolism was more important than age, sex or BMD. The influence of OC suppression on the occurrence of low-traumatic fractures was dependent on the high cortisol level.

Based on the available data and relevant literature review, the chapter concluded that patients with CS are exposed to a very high risk of sustaining severe multiple fractures that cannot be explained by BMD loss measured by DXA. The only predictor of low traumatic fractures is the severity of hypercortisolism itself. Hypercortisolism causes disturbances in the bone remodeling markers: the suppression of bone formation and, to some extent, the uncoupling of bone remodeling. The alteration of the key molecules related to the osteoblastogenesis and osteoclastogenesis pathways provides a link to the pathogenesis of glucocorticoid-induced osteoporosis and adds value to its future successful treatment. Among the existing treatments, bisphosphonates seem to be effective and relatively safe. Treatment with ibandronate intravenously did not have any deleterious effects on pregnancy or the fetus in the described clinical case.
(Imprint: Nova)