Patient-specific bone modelling and remodelling simulation of hypoparathyroidism based on human iliac crest biopsies

Abstract

We previously developed a load-adaptive bone modelling and remodelling simulation model that can predict changes in the bone micro-architecture as a result of changes in mechanical loading or cell activity. In combination with a novel algorithm to estimate loading conditions, this offers the possibility for patient-specific predictions of bone modelling and remodelling. Based on such models, the underlying mechanisms of bone diseases and/or the effects of certain drugs and their influence on the bone micro-architecture can be investigated. In the present study we test the ability of this approach to predict changes in bone micro-architecture during hypoparathyroidism (HypoPT), as an illustrative example. We hypothesize that, apart from reducing bone turnover, HypoPT must also lead to increased osteocyte mechanosensitivity in order to explain the changes in bone mass seen in patients. Healthy human iliac crest biopsies were used as the starting point for the simulations that mimic HypoPT conditions and the resultant micro-architectures were compared to age-matched clinical HypoPT biopsies. Simulation results were in good agreement with the clinical data when osteocyte mechanosensitivity was increased by 40%. In conclusion, the results confirm our hypothesis, and also demonstrate that patient-specific bone modelling and remodelling simulations are feasible.

Conflict of interest statement

Conflict of interest

All authors have no conflicts of interest.

Copyright © 2012 Elsevier Ltd. All rights reserved.

Figures

Fig. 1

Schematic overview of the proposed mechanisms involved in HypoPT. We hypothesized that low PTH suppresses bone resorption via parathyroid hormone receptor 1 (PTHR1), e.g. due to down-regulation of RANKL and reduced bone formation via coupling factor TGF-β1. In addition, the change in PTH level increases the osteocyte mechanosensitivity, e.g. due to increased calcium influx leading to increased expression of IGF-I.

Fig. 2

Unit load cases that were scaled according to the estimated scaling factors for each biopsy and then used for the bone modelling/remodelling simulations. Stresses represented as distributed forces are applied to the faces of the biopsy in the direction and at the face as indicated by the arrows.

Fig. 3

Bone micro-architecture of the initial (a), adapted (b), and simulated HypoPT with 140% osteocyte mechanosensitivity (c), and clinical HypoPT (d) biopsies.

Fig. 4

Bone resorption and formation dynamics of the HypoPT simulation with osteocyte mechanosensitivity of 100% (a) and 140% (b), respectively. If only bone resorption was suppressed, bone formation did not peak and the net formation was not able to account for the bone mass gained during HypoPT. Increasing also the bone cell mechanosensitivity caused a peak formation explaining the net bone formation.