Bone turnover and mineralisation kinetics control trabecular BMDD and apparent bone density: insights from a discrete statistical bone remodelling model.

ABSTRACT

The mechanical quality of trabecular bone is influenced by its mineral content and spatial distribution, which is controlled by bone remodelling and mineralisation. Mineralisation kinetics occur in two phases a fast primary mineralisation and a secondary mineralisation that can last from several months to years. Variations in bone turnover and mineralisation kinetics can be observed in the bone mineral density distribution (BMDD). Here, we propose a statistical spatio-temporal bone remodelling model to study the effects of bone turnover (associated with the activation frequency Ac . f ) and mineralisation kinetics (associated with secondary mineralisation T sec ) on BMDD. In this model, individual basic multicellular units (BMUs) are activated discretely on trabecular surfaces that undergo typical bone remodelling periods. Our results highlight that trabecular BMDD is strongly regulated by Ac . f and T sec in a coupled way. Ca wt% increases with lower Ac . f and short T sec . For example, a Ac . f = 4 BMU/year/mm 3 and T sec = 8 years result in a mean Ca wt% of 25, which is in accordance with Ca wt% values reported in quantitative backscattered electron imaging (qBEI) experiments. However, for lower Ac . f and shorter T sec (from 0.5 to 4 years) one obtains a high Ca wt% and a very narrow skew BMDD to the right. This close link between Ac . f and T sec highlights the importance of considering both characteristics to draw meaningful conclusion about bone quality. Overall, this model represents a new approach to modelling healthy and diseased bone and can aid in developing deeper insights into disease states like osteoporosis.