Increased loss of bone mass caused by osteoporosis is the most common form of skeletal disease in the elderly and is also the main risk factor for bone fractures in old age. Researchers from Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) have now identified a receptor named PPARβ/δ which contributes to bone development and decomposition. This is a promising area for treating various skeletal diseases. It may be possible to cure osteoporosis in the future. The researchers from Universitätsklinikum Erlangen have published their results in the online edition of Nature Medicine*.
Osteoporosis is more than the main risk factor for the increasing number of bone fractures in old age: it also means that patients are more dependent on care and have higher mortality rates. The disease disturbs the balance between bone development and bone decomposition. Existing therapy strategies include the inhibition of osteoclast cell activity which is responsible for bone decomposition. However, this approach to treatment also inhibits osteoblasts which control bone development and this can lead to interference with natural bone restructuring. This means that current osteoporosis therapy often leads to an unphysiological bone structure which is subject to fractures.
A team of FAU researchers led by Dr. Gerhard Krönke at the Department of Medicine 3 – Rheumatology and Immunology (Head of department: Prof. Dr. Georg Schett) at Universitätsklinikum Erlangen have identified an important approach to a new type of therapy: the receptor is involved in both bone development and decomposition and is a key factor for treating various skeletal diseases.
Restoring the balance between bone development and decomposition
‘If this receptor is missing, osteoporosis occurs much faster,’ explains biologist Carina Scholtysek, who was involved significantly in the project. Conversely, the researchers were also able to demonstrate that medication could be used to activate the receptor and cure osteoporosis completely in the experiment.
The activation of PPARβ/δ does not lead to a simple inhibition of bone decomposition, instead it triggers osteoblasts which restore the balance between bone development and decomposition. This method can help to renew a physiological bone structure in contrast to existing osteoporosis therapies.
Medication under clinical trial
An important discovery made in previous research may help medication to become available soon based on this approach. PPARβ/δ also regulates lipid and cholesterol metabolism. A medication which can activate this receptor is currently under clinical trial for reducing increased blood lipid levels. This would mean that medication could be used in future to treat different diseases such a osteoporosis and increased cholesterol levels.
‘The finding that the PPARβ/δ receptor can affect bone decomposition, bone development and renew the physiological bone structure could mean a real breakthrough in osteoporosis therapy,’ says Dr. Gerhard Krönke, Head of the research group at Universitätsklinikum Erlangen. ‘Our model experiments have shown that osteoporosis may even be curable’.
*Carina Scholtysek, Julia Katzenbeisser, He Fu, Stefan Uderhardt, Natacha Ipseiz, Cornelia Stoll, Mario M Zaiss, Michael Stock, Laura Donhauser, Christina Böhm, Arnd Kleyer, Andreas Hess, Klaus Engelke, Jean-Pierre David, Farida Djouad, Jan Peter Tuckermann, Béatrice Desvergne, Georg Schett, Gerhard Krönke, Nature Medicine, doi: 10.1038/nm.3146
Information for the press:
Dr. Gerhard Krönke
Phone: +49(0) 9131 85 42012