Bone fatigue fractures

13/Nov/2014

a pictogramme with a human doing sports. © Horizons

Hairline fractures appear in bones when they are subjected to repeated mechanical stress. As this microscopic damage is often imperceptible unless the bone actually breaks, it is important to find a method capable of detecting, preventing or even treating it. By Anton Vos

Stress fractures account for almost 20% of all sports injuries. They are caused by chronic mechanical stress imposed on the skeleton and present a specific problem: the precursory injuries are extremely fine cracks which are virtually undetectable using medical x-rays prior to an actual fracture. To learn more about their occurrence and the mechanisms that lead to them spreading in the bone tissue, Claire Acevedo, a post-doctoral researcher at the Lawrence Berkeley National Laboratory (Berkeley University) in California, recently tested a mouse model capable of reproducing and investigating the phenomenon. A publication on the subject is in preparation.

It is in weight-bearing bones such as the tibia, the fibula and the metatarsals that micro-cracks usually appear. They are as fine as a hair and spread slowly. "These stress fractures are particularly insidious because they affect healthy bones and occur in the absence of severe shock", explains Acevedo. Those most susceptible to them are elite athletes (runners, dancers, etc.) and members of armed forces subject to intensive training. In this case, the process of self-healing of the bone is not fast enough to prevent the accumulation of these cracks".

It’s not restricted to athletes, however; incidence increases with age, the risk of osteoporosis, the presence of certain diseases such as osteogenesis imperfecta (also known as brittle bone disease) or, paradoxically, long term medication against osteoporosis.

Self-repairing

As they are undetectable under traditional medical x-rays, little is still known about the mechanisms of stress fractures in the complex micro-structure of bones. The only way to study their origins and their evolution as well as the ability of bone to resist and to repair itself is to conduct experiments on live animals. For this, Acevedo has chosen the mouse. "The micro-structure of the bones of pigs or dogs would be more similar to that of the human bone", she says. "But those experiments would have been much more complicated to set up and would take more time than working with rodents".

The animal tests were conducted in collaboration with the AO Foundation in Davos and the EPFL. The first series of tests on dead mice concentrated on evaluating the parameters of resistance of the tibia, by subjecting it to cyclic loads which mimicked the daily forces exerted on an athlete’s skeleton.

Acevedo used synchrotron x-rays, which offer a significantly higher resolution than medical imaging. This method made it possible to observe the initial stage and the propagation of micro-cracks. At the same time, she has also developed a digital three-dimensional model of the mouse tibia. Using this, she deduced that the origin of preference for stress fractures corresponds with areas of concentrated stress determined by the shape as well as the micro-architecture of the bone.

She was also able to identify another point of origin for micro-cracks: irregularities in the surface of the compact bone, including small channels (containing nerves or blood vessels). From there, they propagate through the most fragile areas, via other channels and small cavities. But, thanks to its complex micro-structure, the bone has an ingenious device to stop or deflect the advance of micro-cracks.

In a second test, Acevedo subjected a dozen live – and anaesthetised – rodents to mechanical stress conditions similar to those resulting in a fractured bone. Well before any bones would break, the animals entered a rest period (varying between 0 and 14 days), after which their skeletons were analysed. "As laboratory x-rays cannot render the microscopic lesions, it was difficult to know if the tibia started to fissure while the mice were alive", she points out. "Fortunately, we gathered the results we wanted at the first trial".

Tomorrow’s world

Using measurements from a laser scanning confocal microscope, she was able to observe not only the presence of diffuse damage – the kind that would lead to hairline fractures - at different stages of development but also the process of self-healing in the form of bone material production. "This is one of our main findings", she says. "It suggests that even diffuse damage, usually considered as too insignificant to signal to the bone to repair itself, does actually play a role in the activation of self-repair mechanisms".

The aim of these studies is to develop a method of detecting, preventing or even treating these stress injuries before they cause actual fractures in humans. Whilst this goal still belongs to tomorrow’s world, Acevedo was able to prove her mouse model capable of reproducing a certain number of bone fatigue effects and in a reasonably short period of time. Such a tool will allow her to continue her scientific work and to improve our understanding of the phenomenon.

"Today, one of the only effective treatments available is total rest to allow the bone to heal itself", she says. Not one or two days but at least several weeks. A person suffering from micro-cracks will at some stage feel considerable pain, which should be seen as a kind of warning. "If that person takes a pain reliever and continues their training programme, instead of stopping and resting, then any micro-cracks will accumulate only to end in a full fracture".


(From "Horizons" no. 102, September 2014)

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