gms | German Medical Science

Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2017)

24.10. - 27.10.2017, Berlin

OPG /RANKL signaling in osteocytes correlate with bone structural changes in a sheep model of osteoporosis

Meeting Abstract

  • presenting/speaker Thaqif El Khassawna - Institut für Experimentelle Unfallchirurgie, Justus-Liebig-Universität Gießen, Gießen, Germany
  • Wolfgang Böcker - Klinik und Poliklinik für Unfallchirurgie, Universitätsklinikum Gießen-Marburg, Standort: Gießen, Institute für Experimentelle Unfallchirurgie, Uni. Gießen, Gießen, Germany
  • Deeksha Malhan - Institut für Experimentelle Unfallchirurgie, Justus-Liebig-Universität Gießen, Gießen, Germany
  • Diaa Eldin Daghma - Institut für Experimentelle Unfallchirurgie, Justus-Liebig-Universität Gießen, Gießen, Germany
  • Sabine Stötzl - Institut für Experimentelle Unfallchirurgie, Justus Liebig Universität Gießen, Gießen, Germany
  • Stefanie Kern - Institut für Experimentelle Unfallchirurgie, Justus Liebig Universität Gießen, Gießen, Germany
  • Katrin Susanne Lips - Institut für Experimentelle Unfallchirurgie, Justus-Liebig-Universität Gießen, Gießen, Germany
  • Christian Heiß - Universitätsklinikum Gießen, Klinik für Unfallchirurgie, Gießen, Germany

Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2017). Berlin, 24.-27.10.2017. Düsseldorf: German Medical Science GMS Publishing House; 2017. DocGR25-745

doi: 10.3205/17dkou597, urn:nbn:de:0183-17dkou5978

Veröffentlicht: 23. Oktober 2017

© 2017 El Khassawna et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.


Gliederung

Text

Objectives: Osteoporosis is a systemic skeletal disease defined by loss of bone density resulting in a decreased Bone Mineral Content (BMC), Bone Mineral Density (BMD), and inferior bone microstructure. The effect of glucocorticoids administration causes decreased bone formation and substandard matrix mineralization. The role of osteocytes is frequently addressed with focus on osteoclastogenesis regulation RANKL. However, the quantification of RNAKL and OPG signaling in osteocytes was not studied in sheep. The current study reproduced sheep model of osteoporosis to study the RANKL/OPG ratio correlation to the method of osteoporosis induction.

Methods: 32 female Marino sheep (average 5.5 years) were divided into 4 groups; 1) non-operated control group (K group), 2) bilaterally Ovariectomized (O group); 2) bilaterally ovariectomized and treated with special diet deficient of calcium and Vitamin D (OD group), and 4) in addition to treatment of OD this group received a biweekly dosage of glucocorticoid treatment (ODS group). Iliac crest biopsies and the second lumber vertebrae were collected after 8 months of treatment.

Results and Conclusion: The present study showed trabecular thinning, higher numbers of apoptotic osteocytes and imbalanced metabolism leading to defective mineralization. The global RANKL/OPG ratio in the spine reflect a balanced RANKL/OPG driven bone resorption indifferent to that of the control. Interestingly, assessment of osteocytes-specific RANKL/OPG ratio showed that in its late progressive phase, the steroid-induced osteoporosis stimulates RANKL expression in osteocytes (Fig.1).

Osteoporosis induction in sheep model was described to be more successful when steroid administration is combined with ovariectomy and limited diet. Nevertheless, the understanding of the cellular and molecular interplay is the preceding step to the design of biomaterials or systemic therapeutics. The study showed that serum concentration and the globally calculated RANKL/OPG ratio do not reflect the osteocyte regulation of osteoclastogenesis. RANKL is suggested to induce Sclerostin expression in osteocytes. The osteocyte-specific increased signaling reported in this study can contribute to further explaining the success of Sclerostin antibodies in treating osteoporotic patients despite an increased Osteocyte-expressed RANKL.