Effect of Temporal Changes in Bone Turnover on the Bone Mineralization Density Distribution: A Computer Simulation Study

The heterogeneous distribution of mineral content in trabecular bone reflects the continuous renewal of bone material in bone remodeling and the subsequent increase in mineral content in the newly formed bone packets. The bone mineralization density distribution (BMDD) is typically used to describe this nonuniform mineral content of the bone matrix. Our mathematical model describes changes of the BMDD of trabecular bone as a function of bone resorption and deposition rates and the mineralization kinetics in a newly formed bone packet. Input parameters used in the simulations were taken from experimental studies. The simulations of the time evolution of the BMDD after increase in bone turnover (perimenopausal period) resulted in a shift of the BMDD toward lower values of the mineral content. Transiently, there was a broadening of the BMDD configuration partly showing two peaks, which points to a strongly heterogeneous distribution of the mineral. Conversely, when the remodeling rate was reduced (antiresorptive therapy), the BMDD shifted toward higher values of the mineral content. There was a transient narrowing of the distribution before broadening again to reach the new steady state. Results from this latter simulation are in good agreement with measurements of the BMDD of patients after 3 and 5 yr of treatment with risedronate. Based on available experimental data on bone remodeling, this model gives reliable predictions of changes in BMDD, an important factor of bone material quality. With the availability of medications with a known effect on bone turnover, this knowledge opens the possibility for therapeutic manipulation of the BMDD.