Long-term prediction of three-dimensional bone architecture in simulations of pre-, peri- and post-menopausal microstructural bone remodeling.

Abstract

The mechanical behavior of trabecular bone depends on the internal bone structure. It is generally accepted now that the trabecular bone structure is a result of a load adaptive bone remodeling. The mathematical laws that relate bone remodeling to the local state of stress and strain, however, are still under investigation. The aim of this project was to investigate if changes in the trabecular architecture as observed with age-related bone loss and osteoporosis can be predicted from a computer model that simulates bone resorption after hormone depletion based on realistic models of trabecular microstructure using micro-computed tomography (muCT). A compact desktop muCT providing a nominal isotropic resolution of 14 mum was used to measure two groups of seven trabecular bone specimens from pre-menopausal and post-menopausal women respectively. A novel algorithm was developed to simulate age-related bone loss for the specimens in the first group. The algorithm, also referred to as simulated bone atrophy (SIBA), describes a truly three-dimensional approach and is based directly on cellular bone remodeling with an underlying realistic time frame. Bone resorption is controlled by osteoclastic penetration depth and bone formation is governed by the efficiency level of the osteoblasts. The simulation itself describes an iterative process with a cellular remodeling cycle of 197 days. Activation frequency is controllable and can be adjusted for the different phases of pre-, peri- and post-menopause. For our simulations, osteoblastic and osteoclastic activities were in balance until the onset of menopause, set to be at the age of 50 years. In that period, the structure remained almost constant. After the onset of menopause an imbalance in the cell activities was modeled resulting in a net bone loss. The doubling of the activation frequency in the peri-menopausal phase caused a pronounced loss. Using advanced animation tools and quantitative bone morphometry, the changes in bone architecture associated with the bone loss were monitored over an average observation time of 43 years until the age of 80 years. In that time, bone volume density decreased monotonously with the progression of the simulation for all specimens. Right after the onset of menopause, bone was lost fast, where with the progression of age losses slowed down. The structures at the end-point of the simulations were then compared qualitatively and quantitatively to the structures of the post-menopausal group with all morphometric indices being within a narrow margin of error. These results suggest the feasibility of transforming "normal" to "osteopenic" bone on a microstructural level yielding in realistic bone models similar in appearance as well as in structural behavior if compared to a post-menopausal group of women.