Quantification of remodeling parameter sensitivity--assessed by a computer simulation model

During normal aging and menopause, cancellous bone is lost at all skeletal sites due to remodeling-related factors: negative formation balance; temporarily increased remodeling space; and osteoclastic perforations. The relative importance of the various factors in inducing bone mass loss and perforations is still controversial. We have previously used a computer simulation model to describe the effect of several bone remodeling parameters on vertebral cancellous bone loss. The model focused on two different scenarios for the menopause and three different treatment regimens. The aim of the present study was to extend the previous study by quantifying remodeling parameter sensitivity for changes in the bone mass with the use of the computer model we had previously formulated. The menopause scenario, with increased activation frequency and increased resorption depth, was chosen as the base case scenario, and the following parameters were investigated in the sensitivity analysis: activation frequency; formation balance; resorption depth; and critical trabecular thickness. Simulations were performed for a period of 20 years starting at the age of 48 years. The analysis showed that the number of perforations and the perforation-related mass loss both exhibited a large sensitivity toward variations in the final resorption depth. However, the formation balance was the factor that was responsible for the greater part of the bone mass loss. The computer model allowed us to quantify the sensitivity of different output variables with respect to changes in some of the model parameters. This can give information about the biological mechanisms responsible for bone mass loss around the surgically induced or natural menopause and also provide an indication of the type of treatment that would be most useful in preventing the deterioration of the cancellous network.