Trabecular bone remodelling under pathological conditions based on biochemical and mechanical processes involved in BMU activity

Abstract

In adulthood, bone tissue is continuously renewed by processes governed by basic multicellular units composed of osteocytes, osteoclasts and osteoblasts, which are subjected to local mechanical loads. Osteocytes are known to be integrated mechanosensors that regulate the activation of the osteoclasts and osteoblasts involved in bone resorption and apposition processes, respectively. After collagen tissue apposition, a process of collagen mineralisation takes place, gradually increasing the effective stiffness of bone. This study presents a new model based on physicochemical parameters involved in spongy bone remodelling under pathological conditions. Our model simulates the transient evolution of both geometry and effective Young's modulus of the trabeculae, also taking turnover into account. Various loads were applied on a trabecula in order to determine the evolution of bone volume fraction under pathological conditions. A parametric study performed on the model showed that one key parameter here is the kinetic constant of hydroxyapatite crystallisation. We subsequently tested our model on a pathological case approaching osteoporosis, involving a decrease in the number of viable osteocytes present in bone. The model converges to a lower value ( − 5%) for bone volume fraction than with a normal quantity of osteocytes. This useful tool offers new perspectives for predicting bone remodelling deficits on a local scale in patients with pathological conditions such as osteoporosis and in bedridden patients, as well as for astronauts subjected to weightlessness in space.

Keywords::

• osteocytes
• osteoclast
• osteoblast
• bone pathology
• mineralisation

Acknowledgements

The authors gratefully acknowledge the financial support of this work by the University of the Mediterranean, Aix-Marseille. We thank Professor Argenson and Dr Parrate (of the Surgical Ward of Ste Marguerite Hospital, Marseille) for helpful discussions and Marjorie Sweetko for English language revision. This research was also supported in the framework of the ANR BIOPRO (advanced mechanical approaches to normal and pathological bone remodelling processes) project (reference number: ANR_08_BLAN_0169_02).