Glucocorticoids, inflammation and bone loss

Published on July 30, 2015   28 min

Other Talks in the Series: Bone in Health and Disease

Please wait while the transcript is being prepared...
My name is Christian Roux. I am a professor of Rheumatology in the Paris Descartes University in Paris, France. And the topic today is about bone loss and osteoporosis in patients with inflammatory diseases, receiving glucocorticoids.
Here are my disclosures, related to this talk.
Glucocorticoids are very effective in a number of diseases with acute or chronic inflammation. At any time, roughly 1% of the world population is receiving oral glucocorticoids, and the highest prevalence of use is in patients at the age of 70. That is to say, we are underlying quite high risk of osteoporosis.
Glucocorticoids therapy is the most common cause of secondary osteoporosis. This is a theoretical curve of change in bone strength in patients receiving such a treatment. As you can appreciate, the decrease is rapid and dramatic within the first year, and maybe during the first month after initiating the treatment. And then, this decrease occurs more slowly, there after. This rapid effect is parallel with the risk of fractures, which increases rapidly after the initiation of therapy. And there is a strong rationale for this effect, related to both the underlying effect of inflammation, that we will see on one the slides, but also the effect of steroids on bone through direct or indirect mechanisms.
Here's a summary of these effects of glucocorticoids on bone. And first of all, the first mechanism is direct. Through a direct effect on osteoblasts, and osteocytes, with a decrease of a function of this, as an increase in the apoptosis of these cells. That is to say a direct effect on the capacity of bone formation. There is also an effect on osteoclasts, with and increase of osteoclast activity through the wrong ligand system. And of course, you have, then, increase in bone formation and increase in bone resorption, which is a deleterious and coupling phenomenon on bone remodeling, with an increase in risk of fracture. Here is also an illustration of indirect effect, through the neuroendocrine systems, mainly the GH/IGF-1 axis, and also the decrease in sex steroids, which is well known in the clinical aspect and of these patients. The next point is the effect on calcium metabolism, with a decrease in the intestinal absorption of calcium. There is a debate about the role of secondary hypothyroidism, but it doesn't look to be an important mechanism in the bone fragility in these patients. A very important one, in contrast, is the effect on muscle. It has been shown proteolysis of myofibrils, and the myopathy is in the elderly patients, or in patients receiving massive dose of glucocorticoids, a huge determinant of muscle weakness, risk of falls, and then increase risk of fracture. So certainly, we should not neglect this point on muscle, when we are considering general musculo-skeletal fragility. But again, the main effect is the direct effect of glucocorticoids on bone cells, and mainly upper bone formation. And to demonstrate that, we have this very elegant study conducted