Development of 41 Ca-Based Pharmacokinetic Model for the Study of Bone Remodelling in Humans

Background and Objective: Initial studies show that 41 Ca may be employed as a useful diagnostic bioassay for monitoring metabolic bone disease and its treatment management. The 41 Ca-based pharmacokinetic model is developed to assess its feasibility in monitoring bone disease and clinical responsiveness to therapeutic regimens. Methods: A four-compartment calcium kinetic model is developed to interpret the results of clinically measured 41 Ca tracer kinetics for oral and intravenous dose. This model is extended to simulate changes in bone turnover due to osteoporosis by using Gompertzian function with and without cellular accommodation. The rate constants obtained by fitting to the experimental data on drug intervention are used to simulate the impact of strategic treatment intervention. Results: The present model fits well with the available experimental data on 41 Ca tracer kinetics. In the simulated osteoporotic model, the negative bone balance (i.e. bone loss) reflected by 41 Ca/Ca urine ratio is used to demonstrate slow/fast increase over time compared to the normal state. The cellular accommodation impact is reflected by a recovery from perturbed balance. The model’s predictive ability on the impact of therapeutic intervention is verified using published experimental data. The effect of bisphosphonate intervention results in positive bone balance (i.e. bone gain). Conclusion: The four-compartment 41 Ca tracer kinetic model can be flexibly used in the interpretation of results obtained from ongoing clinical studies.