Jan G. Hazenberg

The role of osteocytes and bone microstructure in preventing osteoporotic fractures

The skeleton alters its geometry following trauma, the introduction of artificial defects and of fatigue-induced microcracks. The precise mechanism by which the skeleton adapts remains unclear. Microcracks might directly affect the cell by damaging the osteocyte cell network or causing apoptosis. Bone microstructure may play an important role in these processes by diverting and arresting propagating microcracks and so prevent fracture failure. This paper discusses the effects of microstructure on propagating cracks, how microdamage may act as a stimulus for bone adaptation and its potential effects on bone biochemistry.

The behaviour of microcracks in compact bone.

This paper summarises four separate studies carried out by our group over the past number of years in the area of bone microdamage. The first study investigated the manner by which microcracks accumulate and interact with bone microstructure during fatigue testing of compact bone specimens. In a series of fatigue tests carried out at four different stress ranges between 50 and 80 MPA, crack density increased with loading cycles at a rate determined by the applied stress. Variations in the patterns of microdamage accumulation suggest that that at low stress levels, larger amounts of damage can build up without failure occurring. In a second study using a series of four-pont bending tests carried out on ovine bone samples, it was shown that bone microstructure influenced the ability of microcracks to propagate, with secondary osteons acting as barriers to crack growth. In a third study, the manner by which crack growth disrupts the canalicular processes connecting osteocytes was investigated. Analysis of individual cracks showed that disruption of the canalicular processes connecting osteocytes occurred due to shear displacement at the face of propagating microcracks, suggesting that this may play some role in the mechanism that signals bone remodelling. In a fourth in vivo study, it was shown that altering the mechanical load applied to the long bones of growing rats causes microcrack formation. In vivo microdamage was present in rats subjected to hindlimb suspension with a higher microcrack density found in the humeri than the femora. Microdamage was also found in control animals. This is the first study to demonstrate in vivo microcracks in normally loaded bones in a rat model.

Microdamage detection and repair in bone: Fracture mechanics, histology, cell biology

Bone is an elementary component in the human skeleton. It protects vital organs, regulates calcium levels and allows mobility. As a result of daily activities, bones are cyclically strained causing microdamage. This damage, in the form of numerous microcracks, can cause bones to fracture and therefore poses a threat to mechanical integrity. Bone is able to repair the microcracks through a process called remodelling which is tightly regulated by bone forming and resorbing cells. However, the manner by which microcracks are detected, and repair initiated, has not been elucidated until now. Here we show that microcrack accumulation causes damage to the network of cellular processes, resulting in the release of RANKL which stimulates the differentiation of cells specialising in repair.

The role of osteocytes in functional bone adaptation

Bone adaptation has attracted attention from a number of research disciplines. Mechanical engineers have tried to describe bone adaptation in terms of equations and computational models, clinicians and biologists have made observations of alterations in bone quality and quantity as a result of bed rest, paralysis and pharmaceutical treatments, and biochemists have investigated the signaling pathways and interactions between bone cells. The idea that the external shape and the internal structure of bone adapts to mechanical loading conditions dates back to 1638, when Galileo suggested that the shape of bones was related to mechanical loading. In 1892, Julius Wolff proposed a correlation between bone architecture and mechanical loading. He suggested that the trabecular architecture found in the proximal femur is orientated in the same direction as the stress trajectories that occur there. Roux, a contemporary of Wolff, suggested that bone adaptation was a self-regulating mechanism by which bone attempts to obtain maximum strength with minimum weight (1). By changing the shape of a bone and organising its internal structure, the amount of tissue required for bones to perform their function can be minimized.

How Does Bone Detect Cracks

We conducted work to investigate fatigue cracking and repair in bone, in which we discovered the mechanism by which bone is able to detect the presence of microscopic cracks and thus initiate repair processes. This investigation has made use of theoretical and applied fracture mechanics, in combination with cell biology. It is the first example of a completely-understood mechanism showing how living cells can respond to mechanical stimuli.