In Vitro Modeling of Diurnal Changes in Bone Metabolism.

There is evidence that bone health is closely linked to a functioning circadian rhythm. Most of the evidence comes from mice, which may exhibit some species-specific differences from humans due to their nocturnal lifestyle. To address the current lack of human model systems, the present study aimed to develop an in vitro model system that can represent diurnal changes in bone metabolism.

In silico & in vitro approaches suggest osteoclastogenesis induction underlying fractures in Entrectinib-treated children.

Entrectinib, a potent, CNS-active, TRK and ROS1 inhibitor is associated with occurrence of bone fractures, particularly in pediatric patients. We embarked on computer-guided and experimental investigations to identify the underlying mechanism that should help safe dosing of children receiving this drug. An artificial intelligence (AI)-based approach was used to allow for hypothesis generation regarding drug effects in a clinical setting and mechanistic insights on safety and efficacy.