A dangerous alliance

Erlangen researchers discover how an autoimmune reaction triggers osteoporosis

Autoimmune diseases such as rheumatoid arthritis can cause osteoporosis-like bone changes. These are triggered by a special kind of antibody that is produced already in early stages of the disease. This has been proven by an international consortium led by researchers of Medical Clinic 3 (Director: Prof. Dr. Georg Schett) at Friedrich-Alexander-Universität Erlangen-Nürnberg’s (FAU) Universitätsklinikum (University hospital). The results of their research have now been published in the Journal of Clinical Investigation (16 Apr 2012).

Autoimmune diseases can often be diagnosed in the blood even before the first symptoms become apparent. These are antibodies against a patient’s own tissue (auto-antibodies), for example against citrullinated proteins (CCP antibodies), which are routinely checked for in blood tests. Two thirds of all rheumatology patients have CCP antibodies. It is precisely these patients that exhibit severe joint and bone damage, caused by increased activity of bone-eating cells. It was previously unknown whether there is a connection between the CCP antibodies and the bone-eating cells (osteoclasts). Now the researchers from Erlangen have succeeded in proving that CCP antibodies directly stimulate the the formation of osteoclasts, thus causing osteoporotic bone changes even before the onset of the disease.

Their findings show that CCP antibodies can recognise protein structures on osteoclasts, stimulate the formation of these bone-eating cells and lead to an imbalance in the bone remodelling process. The connection between CCP antibodies and increased bone resorption has already been clinically observed in numerous patient groups. ‘The mechanism was previously completely unknown, however,’ says Ulrike Harre, a doctoral candidate at Medical Clinic 3 and lead author of the paper.

In order to examine the effect of these antibodies on bone metabolism, the scientists compared patients with rheumatoid arthritis with and without CCP antibodies. This revealed that patients with these antibodies suffer from significantly higher rates of bone resorption. The working group was able to prove in experimental examinations that the CCP antibodies directly stimulate the formation of bone-eating cells and that the large amount of these cells causes more severe damage to the bone. Thus they were able to show how autoimmune diseases lead to bone destruction. The alliance between the immune system and the bones is doubly dangerous: on the one hand, the body attacks itself by responding with inflammation; on the other hand, osteoclast formation leads to osteoporosis.

Further information for the press:

uni | media service | research No. 24/2012 on 13.6.2012