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Chair of orthopedic

Osteoporosis / Osteomalacia / Fibrous Dysplasia and Phosphate Metabolism


FGF23 and sFRP4 in bone healing and regeneration – Serum-Markers in inflammation associated osteoporosis and in fracture healing?

in Cooperation with with the Department of Nuclear Medicine University Würzburg, the Center for Musculoskeletal Surgery Charité Berlin and #Universita La Sapienzia, Rome

Lothar Seefried, Regina Ebert, Birgit Mentrup, Doris Schneider, Susanne Wiesner, Bettina Hafen, Norbert Schuetze, Georg Duda, Paolo Bianco, Franz Jakob

The metabolic pathway of phosphate metabolism and its regulation are not entirely characterized. During recent years some progress could be achieved through the molecular clarification of rare diseases like oncogenic osteomalacia and fibrous Dysplasia. The phosphatonins FGF23 und sFRP4 were described and as such important components of phosphate metabolism were identified. FGF23 can be measured in serum. It is elevated in various bone and joint diseases like arthritis and renal osteopathy and it substantially contributes to pathology in fibrous dysplasia. Both FGF23 and sFRP4 inhibit renal 1alpha-hydroxylase and thus cause osteomalacia. Osteoblast precursors secrete the FGF23 polypeptide, inactivation is achieved via partial proteolysis. Inheritable loss-of-function and gain-of-function mutations of FGF23 cause renal phosphate wasting and familial tumoral calcinosis respectively. We find elevated FGF23-levels during bone healing. This indicates a role of FGF23 in bone healing within a certain window of time. Our objections are to further characterize the physiology and pathophysiology of the protein and to evaluate if a subgroup of osteoporosis patients – with special respect to inflammation associated osteoporosis – displays alterations in phosphate metabolism. Our clinical studies are closely related to the experimental projects.


Literature

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