The Clinical Biomechanics Award 2012 - presented by the European Society of Biomechanics: large scale simulations of trabecular bone adaptation to loading and treatment.
BACKGROUND
Microstructural simulations of bone remodeling are particularly relevant in the clinical management of osteoporosis. Before a model can be applied in the clinics, a validation against controlled in vivo data is crucial. Here we present a strain-adaptive feedback algorithm for the simulation of trabecular bone remodeling in response to loading and pharmaceutical treatment and report on the results of the large-scale validation against in vivo data.


METHODS
The algorithm follows the mechanostat principle and incorporates mechanical feedback, based on the local strain-energy density. For the validation, simulations of bone remodeling and adaptation in 180 osteopenic mice were performed. Permutations of the conditions for early (20th week) and late (26th week) loading of 8N or 0N, and treatments with bisphosphonates, or parathyroid hormone were simulated. Static and dynamic morphometry and local remodeling sites from in vivo and in silico studies were compared.


RESULTS
For each study an individual set of model parameters was selected. Trabecular bone volume fraction was chosen as an indicator of the accuracy of the simulations. Overall errors for this parameter were 0.1-4.5%. Other morphometric indices were simulated with errors of less than 19%. Dynamic morphometry was more difficult to predict, which resulted in significant differences from the experimental data.


CONCLUSIONS
We validated a new algorithm for the simulation of bone remodeling in trabecular bone. The results indicate that the simulations accurately reflect the effects of treatment and loading seen in respective experimental data, and, following adaptation to human data, could be transferred into clinics.
Institute for Biomechanics, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland.
Alina
A
Levchuk
Institute for Biomechanics, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland.
Alexander
A
Zwahlen
Institute for Biomechanics, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland.
Claudia
C
Weigt
Institute for Biomechanics, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland.
Floor M
FM
Lambers
Institute for Biomechanics, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland.
Sandro D
SD
Badilatti
Institute for Biomechanics, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland.
Friederike A
FA
Schulte
Institute for Biomechanics, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland.
Gisela
G
Kuhn
Institute for Biomechanics, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland. Electronic address: ram@ethz.ch.
Ralph
R
Müller
D000222:Adaptation, Physiological; D000465:Algorithms; D000818:Animals; D001363:Awards and Prizes; D016723:Bone Remodeling / Q000502:physiology; D003198:Computer Simulation; D005060:Europe; D049674:History, 21st Century; D051379:Mice; D008954:Models, Biological; D010024:Osteoporosis / Q000503:physiopathology; D012958:Societies, Scientific / Q000266:history; D012986:Software Validation; D016474:Weight-Bearing / Q000502:physiology
Bone remodeling; In vivo validation; Mechanical loading; Pharmaceutical treatment; Simulation