02605nas a2200445   4500000000100000000000100001008004100002260001200043653001000055653001200065653001800077653002000095653001900115653002300134653002800157653002000185653001500205653002700220653002200247653002200269653002600291653002100317653001100338653002500349653001600374653001500390653001600405653001500421653003000436100001900466700002300485700002600508700002200534700002300556245013600579300001400715490000700729520140900736022001402145       2020                            d  c2020-1210a2D/3D10aAnimals10aBone Diseases10aBone Remodeling10aBone and Bones10aCell Communication10aCell Culture Techniques10aCells, Cultured10aCo-culture10aDisease Models, Animal10aEndothelial Cells10aEndothelial Cells10aEx vivo bone cultures10aFracture Healing10aHumans10aOsteoblast/osteocyte10aOsteoblasts10aOsteoclast10aOsteoclasts10aOsteocytes10aTissue Culture Techniques1 aSabrina Ehnert1 aHelen Rinderknecht1 aRomina H. Aspera-Werz1 aVictor Häussling1 aAndreas K. Nussler00aUse of in vitro bone models to screen for altered bone metabolism, osteopathies, and fracture healing: challenges of complex models  a3937-39580 v943 aApprox. every third hospitalized patient in Europe suffers from musculoskeletal injuries or diseases. Up to 20% of these patients need costly surgical revisions after delayed or impaired fracture healing. Reasons for this are the severity of the trauma, individual factors, e.g, the patients' age, individual lifestyle, chronic diseases, medication, and, over 70 diseases that negatively affect the bone quality. To investigate the various disease constellations and/or develop new treatment strategies, many in vivo, ex vivo, and in vitro models can be applied. Analyzing these various models more closely, it is obvious that many of them have limits and/or restrictions. Undoubtedly, in vivo models most completely represent the biological situation. Besides possible species-specific differences, ethical concerns may question the use of in vivo models especially for large screening approaches. Challenging whether ex vivo or in vitro bone models can be used as an adequate replacement for such screenings, we here summarize the advantages and challenges of frequently used ex vivo and in vitro bone models to study disturbed bone metabolism and fracture healing. Using own examples, we discuss the common challenge of cell-specific normalization of data obtained from more complex in vitro models as one example of the analytical limits which lower the full potential of these complex model systems.  a1432-0738