Prednisone prevents particle induced bone loss in the calvaria mouse model
Michael M. Schündeln,
Jakob Höppner,
Felix L. Meyer,
Wiebke Schmuck,
Max D. Kauther,
Gero Hilken,
Bodo Levkau,
Martina Rauner,
Corinna Grasemann
Affiliations
Michael M. Schündeln
Division of Pediatric Hematology and Oncology, Department of Pediatrics III, University Hospital Essen, University of Duisburg-Essen, Germany; Corresponding author.
Jakob Höppner
Department of Pediatrics and CeSER, Katholisches Klinikum Bochum, Ruhr-University Bochum, Bochum, Germany
Felix L. Meyer
Department of Pediatrics II, University Hospital Essen, University of Duisburg-Essen, Germany
Wiebke Schmuck
Department of Pediatrics II, University Hospital Essen, University of Duisburg-Essen, Germany
Max D. Kauther
Department of Trauma-, Hand- and Reconstructive Surgery, University Hospital Essen, Germany; Department for Orthopedics, Agaplesion Diakonieklinikum, Rotenburg Wümme, Germany
Gero Hilken
Central Animal Laboratory, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
Bodo Levkau
Institute for Molecular Medicine III, University Hospital Düsseldorf and Heinrich-Heine-University Düsseldorf, Germany
Martina Rauner
Department of Medicine III, Dresden Technical University Medical Center, Dresden, Germany
Corinna Grasemann
Department of Pediatrics and CeSER, Katholisches Klinikum Bochum, Ruhr-University Bochum, Bochum, Germany; Department of Pediatrics II, University Hospital Essen, University of Duisburg-Essen, Germany
Introduction: Glucocorticoids are essential in the treatment of many chronic inflammatory and malignant diseases but are known to have detrimental effects on bone. This study aimed to investigate the effects of prednisone on osteoclast functioning in vivo in the calvaria particle-induced bone loss mouse model. Methods: 12-week-old male C57BL6/J mice received subcutaneously implanted prednisone (2.5 mg/d, 60 day release (n = 14)) or placebo pellets (n = 10). Osteolysis of the calvaria bone was induced two weeks later by application of ultra-high-molecular-weight polyethylene- (UHMWPE) particles to the dome (vs sham operation). The extent of osteolysis was determined histologically and by micro-computer tomography. Results: Prednisone significantly inhibited particle-induced osteolysis in the skull. No significant difference in osteoclast numbers was seen in mice with prednisone vs placebo treatment. Prednisone treatment alone without particle application did not reduce bone mineral density or deterioration in bone microarchitecture parameters. Conclusions: The calvaria particle-induced bone loss mouse model can be adapted to investigate osteoclast activity in vivo and the effect of prednisone on osteoclasts. In this preventive experimental design, the application of short-term low-dose prednisone has osteoprotective effects without measurable systemic side effects on bone parameters.
