Recent Advances in Pharmacokinetic-Pharmacodynamic (PK-PD) Models of Osteoporosis – Pathways to optimise and exploit existing drug treatments
Abstract: Osteoporosis (OP) is a chronic bone disease which is characterised by bone mass loss and changes in the bone matrix properties which can ultimately lead to bone fracture. There are various forms of OP, which can be related to aging, menopause or the consumption of certain drugs (e.g., corticosteroids, hormonal contraceptives, etc.). With the increase of the elderly population, age-related OP in particular poses a serious health issue which puts large pressure on health care systems.
A major challenge for development of new drug treatments for OP and evaluation of the efficacy of existing treatments is due to current regulatory requirements which demand testing of drugs based on bone mineral density (phase 2 trials) and fracture risk (phase 3 trials). This requires large clinical trials to be conducted and for long time periods, which is very costly.
This, coupled with the fact that many drugs are already available for the treatment of OP, makes the development of new drugs inhibitive. Furthermore, an increased trend of the use of combined drug therapies has been observed in OP management, e.g. sequential anabolic-anticatabolic drug treatment or switching from one anticatabolic drug to another. Conducting clinical trials for combined therapies is either unfeasible or impractical due to the large number of combinatorial possibilities.
Alternatively, the use of in silico pharmacokinetic-pharmacodynamic (PK-PD) models of OP treatments can help to inform clinical drug usage by identifying the most promising combinations to be tested clinically in confirmatory trials rather than exploratory only trials. These in silico trials can also help to optimise trial design and identify subgroups of the population that show benefit-risk profiles (both good and bad) that are different from the average patient. In this lecture, several important topics will be discussed: bone physiology, OP, current drug treatments and bone mineral density (BMD) prediction using state-of-the-art mechanobiological PK-PD models of OP treatments.
Biosketch: He is a professor of Mechanical Engineering (since 12/2021) at the University of Seville (US).His research has been devoted to Biomechanics throughout his career, focusing on different topics such as: Multibody System Dynamics, viscoelasticity of soft tissues, bone micromechanics, FE simulation of human mastication and dental implants,
biomechanical analysis of pelvic fracture fixation and numerical models of bone adaptation. Currently, he is developing numerical models of bone adaptation based onbone cell population models in collaboration with Professor Pivonka of the Queensland University of Technology (QUT). He was a Vice-head of the Department of Mechanical Engineering and Manufacturing (04/2018to 04/2022). Also, he was a President of the Organizing Committee of the 23 rd Congress of the ESB.
