Adjuvant drug-assisted bone healing: Part I – Modulation of inflammation

Issue title: Bone Healing

Guest editors: J. Pietzsch and F. Jung

Article type: Research Article

Authors: Rothe, Rebecca^a | Schulze, Sabine^{b; c} | Neuber, Christin^a | Hauser, Sandra^a | Rammelt, Stefan^{b; c; d; 1; *} | Pietzsch, Jens^{a; e; 1; *}

Affiliations: [a] Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Department of Radiopharmaceutical and Chemical Biology, Dresden, Germany | [b] University Center of Orthopaedics & Traumatology (OUC), University Hospital Carl Gustav Carus, Dresden, Germany | [c] Center for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany | [d] Center for Regenerative Therapies Dresden (CRTD), Dresden, Germany | [e] Technische Universität Dresden, School of Science, Faculty of Chemistry and Food Chemistry, Dresden, Germany

Correspondence: [*] Corresponding authors: Prof. Dr. Stefan Rammelt, University Center for Orthopaedics & Traumatology, University Hospital Carl Gustav Carus, Fetscherstrasse 74, 01307, Dresden, Germany. Tel.: +49 351 4583211; Fax: +49 351 4584307; E-mail: [email protected] and Prof. Dr. Jens Pietzsch, Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Radiopharmaceutical and Chemical Biology, Bautzner Landstraße 400, 01328, Dresden, Germany. Tel.: +49 351 2602622; Fax: +49 351 26012622; E-mail: [email protected].

Note: [1] SR and JP share senior authorship.

Abstract:  Critical-size bone defects after compound fractures, infection, or tumor resection are challenging to treat. The same is true for fractures in patients with impaired bone healing due to metabolic diseases and cancer. Despite considerable progress over the last decade in surgical techniques, material design, and dedicated imaging approaches, these scenarios represent unsolved clinical problems. The high socioeconomic burden of such conditions justifies increasing interest in novel osteoinductive drugs for adjuvant therapeutic approaches. There is an increasing body of experimental and clinical literature on potentially promising effects of growth factors, anti-resorptive, and anabolic agents. The true clinical efficacy of these, however, is discussed controversially. Therefore, we aimed to critically examine the hypothesis that targeted adjuvant therapies have the potential to enhance bone regeneration in critical-size bone defects and under systemic conditions that impair bone healing. This first approach to the topic deals with small molecule drugs and compounds that influence the immune response and inflammatory processes. In particular, literature reporting on selective cyclooxygenase-2 inhibitors has been reviewed with respect to their local and systemic mode of action and to stimulate further research on bone healing under critical conditions.

Keywords: Biomaterials, critical-size bone defects, cyclooxygenase-2, innate immunity, prostanoids, signaling, small molecules

DOI: 10.3233/CH-199102

Journal: Clinical Hemorheology and Microcirculation, vol. 73, no. 3, pp. 381-408, 2019