Although neither quantity of exercise nor MI were significantly associated with stress fracture in this study, a family history of osteoporosis, osteopenia, frequent fracture, or stress fracture was a strong independent predictor for incident injury. Because a stress fracture can be defined as a repetitive stress injury, training volume (ie, amount of exercise), which is directly related to the number of repeated applications (or “strain cycles”), is thought to be a key component in the pathophysiology of stress fracture.30
However, recent evidence31
has re-emphasized the observation that stress fracture results from an imbalance between the microfracture caused by repeated loading cycles and the skeleton’s own response to remodel the damaged region.30,32
Because remodeling is a constant, dynamic process, it may be an inadequate acceleration of this process that results in stress fracture. Therefore, the rate of increase in exercise volume may be a more informative activity parameter than the total volume of exercise as a predictor of stress fracture. Because the reactive forces transmitted from the ground to the skeleton depend on the composition of the playing or training surface, that parameter is also of significant interest. Future studies should examine these and other activity-related factors.
A cohort study of older adolescent Australian track- and-field athletes demonstrated that age at menarche was an independent risk factor for stress fracture, with earlier ages providing significant protection.10
Menarche occurs near the end of the pubertal growth spurt, which is accompanied by a rapid increase in bone mass and BMD, one of the main determinants of a bone’s ability to withstand loading.12,16
Other studies have not consistently replicated this finding, although none have suggested an inverse relationship between age at menarche and risk for stress fracture.26
Numerous small studies have also consistently suggested that stress fractures are less common among athletes with regular menses26
; however, the studies have not been sufficiently large to afford adequate statistical power to reach firm conclusions. The presumed mechanism through which regular menses would offer protection against stress fracture is the improved BMD associated with a normal endogenous estrogen state. In the present study, a small proportion of participants met our a priori definition of MI, all of which were girls with stress fracture, a highly significant statistical finding. However, because the majority of both case and control subjects demonstrated regular menstrual histories, we have emphasized the nonsignificant findings with respect to the expanded MI definition as more clinically relevant.
The lack of significant associations of stress fracture with high activity levels or MI may be because of insufficient statistical power. In this sample, both case and control subjects participated in relatively high levels of activity, thereby reducing the variability in the exposure, which may make it more difficult to detect a real effect on the outcome. The sample size of 168 participants yielded only 10.5% statistical power to detect a difference as small as 0.8 hour/week of activity and 22.4% statistical power to detect the difference in the prevalence in MI (expanded definition). We cannot exclude the possibility that the growing stigma of the female athlete triad led to a much lower proportion of girls reporting MI than expected. An additional limitation of the case-control design is the potential for recall bias; case subjects may have given greater thought to potential causes of their stress fractures, including family history. Thus, this study may have overestimated the magnitude of association between stress fracture and family history of skeletal abnormalities. However, the magnitude of this association was so robust (~3 times the odds of a positive family history among case subjects) that it is unlikely to have been because of recall bias alone.
To further clarify the relationships, we separated a family history of osteoporosis or osteopenia, the measurable indices of skeletal health, from a family history of frequent fractures or frank stress fractures, which are outcomes of the interaction between bone and the loads applied to it. It is noteworthy that this split resulted in only the measurable indices being significantly associated with stress fracture in the female adolescent. Osteoporosis and osteopenia lie on a spectrum of decreased BMD, the majority of which is determined by inherited factors.15
These factors, which are largely unidentified, could be transmitted to the adolescent, thereby increasing her risk for an insufficiency-type stress fracture. The history of an actual fracture depends to some degree on the activity pattern characteristics of the injured family member, few of which may be inheritable.
Although BMI was directly related to BMD in the secondary analysis of case subjects, this variable was not a significantly protective factor for stress fracture in the entire sample. In fact, each unit increase in BMI was associated with an unadjusted 12% increase in the odds of stress fracture. Recent work by Goulding et al33
has suggested that children and adolescents with increased BMI exhibit an increased risk of fracture (at the distal radius). Some have hypothesized that heavier patients in that study, as determined by higher BMI, may have fallen with greater force than normal-weighted individuals, sustaining the traumatic wrist fractures. Others attribute the increased fracture rate to decreased BMD because of lower fitness in children with higher BMI. In athletic individuals, like those in the current cohort, lower fitness levels could translate to injury because of a lesser ability to absorb and withstand the effects of repetitive stresses. In a multivariate model including physical activity and menstrual ratio, however, BMI did not remain significantly associated with stress fracture, perhaps as both physical activity and BMI relate to fitness.
Mean daily intakes of calcium and vitamin D in this sample did not meet the daily recommended intake of 1300 mg for calcium but satisfied the American Academy of Pediatrics recommendation of 200 IU/day of vitamin D for female adolescents. Interestingly, however, neither dietary component was significantly associated with stress fracture.
As mentioned, we are unable to comment on any association between BMD and stress fracture. However, the BMD z score compares participants with a historical cohort of age- and ethnicity-matched female adolescents. A z score of −0.41 would suggest a lower mean BMD among case subjects in this study than among female adolescents in the general population. Although this mean z score is not in a range that elicits significant clinical concern (eg, either less than −1.0 or −2.0, depending on expert opinion), a BMD in active athletes lower than the normal BMD of the general population of female adolescents, many of whom are inactive, is concerning.
Other limitations must be acknowledged and considered. In addition to the potential for recall bias and limited statistical power mentioned earlier, this matched case-control design also precludes the ability to assess the impacts of matching factors age and ethnicity on stress fracture risk. An additional limitation of this study is a lack of generalizability, because the sample is almost entirely white. However, this limitation is mitigated because whites are a group at increased risk for stress fracture,34
so this cohort represents an enriched sample in which to study this particular injury. Similarly, in subgroup analyses of activity type, dance was suggestive of an effect on stress fracture risk in the current study. This finding may be explained by the fact that ballet dancers are particularly prone to the stress fracture of the lumbar spine known as spondylolysis, and the clinic where all of the participants were enrolled is a wellknown referral center for injured dancers.
The homogeneity of the current study sample reflects the characteristics of the population referred to the sports medicine center at this particular children’s hospital: namely, active but generally healthy female adolescents. Given the relatively good levels of nutritional and menstrual health in the study population, many of the exposures potentially predictive of stress fracture in our pathogenetic model were too similar (eg, physical activity and calcium and vitamin D intake), too uncommon (eg, disordered eating and smoking), or both (eg, MI) to detect an effect on the outcome. Other factors known to affect BMD and potentially stress fracture risk, such as medication use and chronic diseases, were specifically excluded from the sample, whereas age was rendered nonpredictive by matching. That leaves heredity and BMI as the only factors potentially predictive of stress fracture in this study. The most proximate causes of stress fracture are thought to be excessive repetitive stress and insufficient load bearing capacity, or “bone strength.” Bone strength is determined by both bone geometry and BMD. Because we did not measure bone geometry in this study, it is not surprising that only the inheritable, but as yet undefined, determinants of BMD account for the variability in stress fracture diagnosis in our clinics. In addition to prospective research that more closely examines the changes in amount and types of weekly exercise, as well as the types of training surfaces over time, studies of the relationship between stress fracture and genetic markers of skeletal health are, therefore, needed.