Glucocorticoid‐induced osteoporosis: lessons from Cushing's syndrome

Abstract

SummaryGlucocorticoid-induced osteoporosis (GIO) is the most frequent form of secondary bone disorders. Most of our knowledge on its pathogenesis and treatment has been obtained by investigating patients treated with exogenous glucocorticoids. This review will focus on the bone disorder in endogenous Cushing's syndrome, updating recent advances in its pathophysiology, diagnostic aspects and the various predictors which are important in determining bone mineral density (BMD) and fracture risk. We now know strong evidence that beside BMD, bone microarchitecture, one of the most important elements of bone quality, is a key factor in determining fracture risk. Recently, two new methods (spinal deformity index and trabecular bone score) have been shown to be useful markers of bone microarchitecture in GIO. Investigations of GIO in endogenous Cushing's syndrome have also contributed to our understanding on its natural history and reversibility. Relying on recently published guidelines for management of exogenous GIO, a short list of suggestions is provided regarding the optimal diagnostic and therapeutic approach to patients with endogenous GIO.

Body composition and bone mineral density in women with Cushing's syndrome in remission and the association with common genetic variants influencing glucocorticoid sensitivity

“…Interestingly, in that study, duration of GC replacement after treatment for CS was independently associated with reduced BMD at lumbar spine. A similar association was observed in our study, i.e., GC replacement therapy was independently associated with reduced total BMD and BMD at lumbar spine, probably explained by the fact that the effects of GCs on the skeletal tissue is most prominent on trabecular bone such as in the lumbar spine (27). The median hydrocortisone dose used in the GC-treated patients in our study was 25 mg/day.…”

Higher Glucocorticoid Secretion in the Physiological Range Is Associated With Lower Bone Strength at the Proximal Radius in Healthy Children: Importance of Protein Intake Adjustment

“…Adjustments for more than only a few biological plausible covariates (fulfilling respective model inclusion criteria) may really be required to “winkle out” a specific direct (not mediated), but physiologically moderate predictor action, which, in case of the GC–bone relationship, has been biologically proven in cell and tissue experiments …”

Treatment of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline

“…The scant fracture data suggest that the increased symptomatic fracture risk disappears after curing CS, similar to that seen in exogenous glucocorticoid-induced osteoporosis (204,206). It is not clear whether complete normalization occurs because the expected BMD for a given person cannot be predicted (8,173,200). We recommend a detailed fracture assessment, evaluating BMD at the spine and hip, obtaining lateral morphometric imaging of the spine, adequate calcium and vitamin D intake, avoidance of excessive glucocorticoid supplementation, and personalized long-term follow-up based on the results of bone evaluation.…”

“…Osteoporosis results from direct effects of cortisol on bone cells and indirect events such as glucocorticoid-induced hypogonadism, secondary hyperparathyroidism, GH deficiency, and reduced bone strain due to myopathy (200). However, the prevalence of fractures is not known (201).…”