Glucocorticoid-induced osteoporosis (GIO) is the most relevant form of secondary osteoporosis and fractures occur in 3050% of individuals. Moreover, glucocorticoids (GC) may cause osteonecrosis in as many as 25% of patients on high-dose or long-term therapy. Bone loss occurs fast and may be as high as 1015% within the first 36 months and preferentially affects bone sites rich in cancellous bone such as the ribs, vertebral bodies and the femoral neck. It appears that there is no safe dose of GC and even inhaled GC in higher doses suppress bone formation and accelerate bone loss.
The effects of GC on bone are primarily direct and here the major effect is on osteoblasts and osteocytes. GC lead to premature apoptosis of these two cell systems and inhibit osteoblastogenesis at the same time. Newer insights into the pathophysiology of GIO has led to the discovery of the importance of the local activity of the 11β-hydroxysteroid dehydrogenase (11β-HSD) system which consists of two isoenzymes determining the local concentration of active cortisol. Various activation of this system is thought to be responsible for the clinical observation whereby patients are more or less prone to the effects of GC. Other important mechanisms i.e. impaired production of IGF-1 and testosterone support the decrease in osteoblastic activity. Although absolute osteoclastic activity does not appear to be increased in GIO it is nevertheless too high when compared to the simultaneous marked decrease in bone formation. Here, the primary driving factor seems to be a decrease in local osteoprotegerin production that allows RANKL to increase osteoclastogenesis and promote osteoclast life span.
The cornerstones of prevention and treatment of GIO include a calcium (12001500 mg) and vitamin D3 supplementation (8001200 IE) as well as a bisphosphonate treatment or, in high-risk patients teriparatide injections.
25 - 29 Apr 2009
European Society of Endocrinology