Kyriacos Eleftheriou outlines a theory as to why some athletes may be at increased riskA stress fracture is a partial or complete fracture of a bone, not associated with a significant traumatic injury, and resulting from the bone’s inability to withstand stress applied in a rhythmic, repeated manner. It is one of the most common and potentially serious overuse injuries (1,2).
The first documented report of a stress fracture was in 1855 by a military doctor, who described soldiers presenting with painful and swollen feet. With the discovery of X-rays in the late 19th century, this phenomenon was shown to be the result of a fracture of the metatarsal bone (the ‘march fracture’). Since then, stress fractures have been reported increasingly in populations involved in repetitive weight-bearing activities, such as athletes, military personnel and dancers. Although stress fractures have been found to occur in most bones, they are most common in weight-bearing extremities, with the tibia usually affected in runners and the foot in soldiers (1,2,3).
The effect of heavy repeated mechanical usage (such as running or marching) causes a buildup of micro-damage in bone. The body responds to this through the process of ‘bone remodelling’, in which damaged/old bone is removed and healthy/new bone is deposited. The two processes of bone remodelling (ie resorption and deposition of bone) occur continuously through our lives, and in normal circumstances there is a balance of the two opposing processes to keep our bones healthy.
At times of increased activity, the rate of both processes increases in an attempt to remove bone damaged by the mechanical stresses and at the same time not only replace this but also deposit the larger amount of bone required to accommodate the increased activity and forces through the skeleton. Although not conclusively shown, there is ample evidence to suggest that in certain individuals, at times of increased or unaccustomed activity, the deposition of new bone lags slightly behind the much faster resorption process. For a short period (a few weeks and dependent on the continuing level of activity) there is a net loss of bone, before the deposition process catches up and starts to increase bone strength. It is believed that this is the period when the bone is vulnerable (especially in the presence of micro-damage), and at risk of developing a stress fracture.
The main mechanical explanations of how stress fractures can occur are not incompatible with this theory. Muscle fatigue has been shown to be a risk factor: it leads to a change in the loading through bones, with increased mechanical stresses in areas that normally would be protected by good muscle function. It is also suggested that muscle overload, in which muscular contraction puts excessive forces through areas of bone, can also lead to stress fracture – again, subjecting areas of bone to unaccustomed mechanical stress.
A number of risk factors have been associated with the development of stress fractures, but the exact causation is likely to be multi-factorial(2, 3). Certainly the type and amount of activity are obvious risks. A number of studies in athletes and military recruits have suggested a variety of other predisposing factors, but the evidence is conflicting. As well as the type, intensity, duration and frequency of activity, other extrinsic factors examined include: the type of shoe worn (eg its age and quality) and the type of training surface used.
An even larger number of factors intrinsic to the athlete may also be implicated. These include age, race, gender, anatomical features such as high foot arches, knock-knees or leg-length discrepancy, characteristics of bone (geometry, density), and health-risk behaviour such as a previous sedentary lifestyle or smoking.
The list is long, and the lack of definitive evidence-based preventative measures underlines our lack of knowledge about whether and by how much a specific factor predisposes an athlete to develop a stress fracture.
Advances in the science of genetics in recent decades have been accompanied by an exponential increase in understanding of how our 30,000 genes interact with the environment to determine not only our physical characteristics, but also our aptitudes, capabilities, vulnerabilities and even our behaviour. In the field of sports, genetic factors have already been shown to be involved in determining one’s sporting prowess, apparent to all from our earliest childhood years, when we recognise the ‘gifted’ athletic offspring of similarly gifted parents. Genes have also been identified that put individuals at risk of a number of disorders, from cardiovascular disease to cancer.
The genetic predisposition to develop a stress fracture is still a largely unexplored area. Nevertheless, the evidence is there. Not only have there been reports of the same individuals developing multiple stress fractures (4-6), but the development of multiple stress fractures in identical anatomical sites in identical twins has also been documented (7).
Furthermore, genetic factors account for up to 50-70% of the variability of bone mineral density (BMD) in the population (8). BMD is, we now know, one of the major determinants in the risk for older people developing an osteoporotic fracture (9). It is not, therefore, surprising that there should be a significant heritability component for the risk of sustaining an osteoporotic fracture: genetic factors constitute up to a third of the risk in such cases (10).
Genes likely to be involved in the development of both osteoporotic and stress fractures would be those that produce or regulate the molecules involved in bone and bone matrix formation, bone remodelling and calcium handling in the body. With various genes being involved in the determination of a number of other of our bodily characteristics (such as the shape of our body and skeleton), it is not unlikely that such genes can therefore indirectly also predispose an individual to develop a stress fracture.
However, osteoporosis and stress fractures are very different conditions. Osteoporotic fractures occur mainly in the elderly, where the main threat to bone strength is BMD. But there are a number of other macro-structural and micro-structural properties (including bone shape, mineralisation pattern, and elasticity) that also play a role in bone strength, and these need to be considered in younger athletes. The mechanisms by which the osteoporotic and stress fractures occur are likely to be different.
The few studies (limited by the small number of subjects investigated) that have looked for a link between specific genes and the development of stress fractures have not produced any positive results. As things stand, the only association established between a gene and the risk for developing a stress fracture has been that for the Vitamin D receptor gene, but the link was a weak one.
Our understanding of the risks that predispose an athlete to develop a stress fracture is still very limited. While there is ample evidence that a genetic predisposition exists, the research has not yet explained the mechanisms at work and any suggested preventive measures and advice to athletes cannot be based on conclusive evidence.
Neither do we yet know how strong the genetic component is, and how it interacts with other predisposing factors, nor have any specific ‘risk’ genes been identified. When this happens, however, we should be much clearer about how stress fractures occur and should also therefore be far better placed to identify and advise the at-risk athlete on how to avoid potentially career-threatening damage.
Kyriacos Eleftheriou is clinical orthopaedic research fellow at University College London