Journal of Biomechanics 40 (2007) 1381–1391 Bone remodelling algorithms incorporating both strain and microdamage stimuli Laoise M. McNamara, Patrick J. Prendergast à Trinity Centre for Bioengineering, School of Engineering, Parsons Building, Trinity College, Dublin 2, Ireland Accepted 8 May 2006 Abstract Biomechanical theories to predict bone remodelling have used either mechanical strain or microdamage as the stimulus driving cellular responses. Even though experimental data have implicated both stimuli in bone cell regulation, a mechano-regulatory system incorporating both stimuli has not yet been proposed. In this paper, we test the hypothesis that bone remodelling may be regulated by signals due to both strain and microdamage. Four mechano-regulation algorithms are studied where the stimulus is: strain, damage, combined strain/damage, and either strain or damage with damage-adaptive remodelling prioritised when damage is above a critical level. Each algorithm is implemented with both bone lining cell (surface) sensors and osteocyte cell (internal) sensors. Each algorithm is applied to prediction of a bone multicellular unit (BMU) remodelling on the surface of a bone trabecula. It is predicted that a regulatory system capable of responding to changes in either strain or microdamage but which prioritises removal of damaged bone when damage is above a critical level, is the only one that provides a plausible prediction of BMU behaviour. A mechanism for this may be that, below a certain damage threshold, osteocyte processes can sense changes in strain and fluid flow but above the threshold damage interferes with the signalling mechanism, or causes osteocyte apoptosis so that a remodelling response occurs to remove the dead osteocytes. r 2006 Elsevier Ltd. All rights reserved. Keywords: Bone; Remodelling; Strain; Microdamage; Mechano-regulation; Mechanobiology 1. Introduction It is generally agreed that the actions of osteoclasts and osteoblasts are coupled during trabecular bone remodelling. Osteoclasts travel along the surface of the trabeculae resorbing tissue and forming a resorption cavity and osteoblasts follow on behind filling in the cavity with new tissue (Parfitt, 1984). The regulatory mechanisms governing the effect of mechanical stress on the action of osteoclasts and osteoblasts are not fully understood; however it seems that mechano- sensitive osteocytes are capable of transducing changes in mechanical stimuli into biochemical signals that regulate cellular responses (El Haj et al., 1990; Burger and Klein-Nulend, 1999; Chambers et al., 1999; Bonewald, 2002). Attempts have been made to determine what exact mechanical stimulus (fluid flow, matrix strain, matrix damage) causes mechanosensitive cells to respond. Experiments have shown that fluid flow activates osteoblasts in monolayer to produce anabolic factors such as prostaglandins and nitric oxide (e.g., Bakker et al., 2003; McGarry et al., 2005). Also osteocyte-like cells have produced biochemical signals in response to fluid flow (Bonewald, 1999). Comparable biochemical re- sponses were not observed in osteocytes attached to substrates undergoing a cyclic stretch, indicating that matrix deformation may play a lesser role in osteocyte stimulation (Owan et al., 1997; You et al., 2000). It has ARTICLE IN PRESS www.elsevier.com/locate/jbiomech www.JBiomech.com 0021-9290/$ - see front matter r 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.jbiomech.2006.05.007 à Corresponding author. Tel.: +353 1 6081383; fax: +353 1 6795554. E-mail address: pprender@tcd.ie (P.J. Prendergast).