Glucocorticoids, inflammation and bone loss

Published on July 30, 2015   28 min
0:00
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.
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Here are my disclosures, related to this talk.
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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.
0:44
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.
1:33
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
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in normal, healthy subjects. So these subjects don't have any inflammation, and they receive a very low dose of steroids. That is to say, five milligram of Prednisone per day. And on this slide here, are shown the results on the bone formation markers, Osteocalcium and PICP, showing that, with a comparison, with the placebo group, the subjects receiving Prednisone at low dose, have actually a rapid decrease in the bone formation markers. Showing that, even in case of normal, baseline bone remodeling, there is an immediate and large decrease in bone formation in these patients. In the same study, it has been shown that there is no relevant change in the intakes parameter, which is the marker of bone resorption. So this is the clinical evidence, I would say, that the most important effect of steroids, even at low dose, is the effect on bone formation. Moving now to the clinical implication of that next slide,
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we know that there is a huge increase in the risk of fractures in patients receiving long term steroids. And this effect is mainly on the trabecular component of bone. That is why the risk of the vertebral fractures is so high. So this is one of the very, very numerous studies on this topic, showed here in a large cohort of Italian subjects receiving long term steroids. That the proportion of patients having at least one vertebral fractures, or at least two vertebral fractures is quite high. And you can appreciate that, according to age, this prevalence is between 30-50% for at least one vertebral fracture. Whatever the underlying disease, because this is true in patients with rheumatoid arthritis, but also in patients with polymyalgia rheumatica, or patients with inflammatory lung diseases. This study has been conducted by systematic spine x-rays in patients for whom, in a majority of cases, the vertebral fracture were ignored, and didn't come to clinical attention.
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Glucocorticoids, inflammation and bone loss

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