Prevention of Bone Destruction by Mechanical Loading Is Not Enhanced by the Bruton's Tyrosine Kinase Inhibitor CC-292 in Myeloma Bone Disease.

Autor: Ziouti F; Department of Internal Medicine II, University Hospital Würzburg, 97080 Würzburg, Germany., Rummler M; Research Centre, Shriners Hospital for Children-Canada, Montreal, QC H4A 0A9, Canada.; Department of Pediatric Surgery, McGill University, Montreal, QC H4A 3J1, Canada;.; Julius Wolff Institute and Berlin Institute of Health Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany., Steyn B; Research Centre, Shriners Hospital for Children-Canada, Montreal, QC H4A 0A9, Canada.; Department of Pediatric Surgery, McGill University, Montreal, QC H4A 3J1, Canada;., Thiele T; Julius Wolff Institute and Berlin Institute of Health Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany., Seliger A; Julius Wolff Institute and Berlin Institute of Health Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany., Duda GN; Julius Wolff Institute and Berlin Institute of Health Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany., Bogen B; Institute of Clinical Medicine, University of Oslo and Department of Immunology, Oslo University Hospital, 0424 Oslo, Norway., Willie BM; Research Centre, Shriners Hospital for Children-Canada, Montreal, QC H4A 0A9, Canada.; Department of Pediatric Surgery, McGill University, Montreal, QC H4A 3J1, Canada;.; Julius Wolff Institute and Berlin Institute of Health Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany., Jundt F; Department of Internal Medicine II, University Hospital Würzburg, 97080 Würzburg, Germany.; Comprehensive Cancer Center Mainfranken, 97080 Würzburg, Germany.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2021 Apr 07; Vol. 22 (8). Date of Electronic Publication: 2021 Apr 07.
DOI: 10.3390/ijms22083840
Abstrakt: Limiting bone resorption and regenerating bone tissue are treatment goals in myeloma bone disease (MMBD). Physical stimuli such as mechanical loading prevent bone destruction and enhance bone mass in the MOPC315.BM.Luc model of MMBD. It is unknown whether treatment with the Bruton's tyrosine kinase inhibitor CC-292 (spebrutinib), which regulates osteoclast differentiation and function, augments the anabolic effect of mechanical loading. CC-292 was administered alone and in combination with axial compressive tibial loading in the MOPC315.BM.Luc model for three weeks. However, neither CC-292 alone nor its use in combination with mechanical loading was more effective in reducing osteolytic bone disease or rescuing bone mass than mechanical stimuli alone, as evidenced by microcomputed tomography (microCT) and histomorphometric analysis. Further studies are needed to investigate novel anti-myeloma and anti-resorptive strategies in combination with physical stimuli to improve treatment of MMBD.
Databáze: MEDLINE
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