In this study, we demonstrate strong positive associations of total lean mass and fat mass with bone density measures in adolescent athletes, particularly EA, and inverse associations of percent trunk fat and trunk to extremity fat ratio (surrogates for visceral fat) with bone density in AA, even after controlling for estrogen status. These data support recent observations of negative associations of visceral fat with bone density in obese adolescents (13
), and extend this finding to a population of young athletes.
Lower BMD in AA in comparison to EA has been well-documented in adult and adolescent studies and has been attributed to a state of estrogen deficiency in amenorrheic women. We have shown that in adolescent athletes, menstrual dysfunction and disordered eating behavior are important determinants of low bone density (4
). In addition, previous studies have demonstrated associations of total fat mass and lean mass with bone density measures (4
). However, the impact of site-specific fat mass on bone has not been thoroughly examined in adolescent athletes, particularly after controlling for lean mass and estrogen status. Total lean mass correlated positively with BMD measurements throughout the body, but in AA, total lean mass was more weakly associated with BMD Z-scores of the hip and WB BMC/Ht than in EA. This suggests that estrogen may be permissive for the positive effects of exercise on bone in athletes. A permissive effect of supplemental estrogen for the beneficial effects of mechanical loading on bone has been similarly reported in post-menopausal women, who are also estrogen deficient (27
We hypothesized that our surrogate measures of subcutaneous fat (total fat mass) and visceral fat (percent trunk fat and trunk to extremity fat ratio) would be positively and negatively associated with BMD, respectively, in our study population. The predicted relationship between total fat mass and BMD was only seen for the lumbar spine and WB BMC/Ht for the group as a whole, and for the lumbar spine in EA. It is possible that the relationship between total fat mass and BMD was attenuated in AA secondary to very low total fat in AA. Additionally, as hypothesized, we found an inverse association of percent trunk fat and trunk to extremity fat ratio with bone density measures in our subjects. Regression modeling supported the independent positive associations of total lean mass and total fat mass, and independent negative associations of percent trunk fat and trunk to extremity fat ratio, with height adjusted bone measures for the whole group.
Recent studies have documented deleterious effects of visceral fat on bone in normal and obese populations (8
), consistent with our findings of the negative correlations of percent trunk fat and trunk to extremity fat ratio (surrogates for visceral fat) with bone density in AA. This is likely a consequence of adipokines and inflammatory fat products secreted by visceral fat that are deleterious to bone (13
). Greater visceral or trunk fat predicts not only a higher risk of the metabolic syndrome, but also lower bone density (30
). Percent trunk fat and trunk to extremity fat ratio did not differ between AA and EA in our study, likely a consequence of similar relative decreases in trunk fat and extremity fat in AA. However, in anorexia nervosa, a more severe energy deficiency state than AA associated with marked reductions in bone density, percent trunk fat and trunk to extremity fat ratio are lower than in controls, indicative of greater relative reductions in trunk fat than in extremity fat (32
One may thus speculate that a decrease in percent trunk fat in conditions of extreme energy deficiency and low bone density may be a protective phenomenon to prevent further decreases in bone density. Decreases in percent trunk fat may not be evident in AA, who are energy deficient, but not to the extent seen in anorexia nervosa. Of note, higher cortisol levels have been associated with higher trunk fat in adult women with anorexia nervosa (33
), and it will be important to examine cortisol levels in adolescent AA to determine whether similar associations are evident in this population, contributing to a preservation of percent trunk fat. Some studies have reported higher levels of cortisol in adolescents who have exercise-induced amenorrhea, compared with eumenorrheic girls (34
). We did not measure cortisol levels in this study; however, this will be important to assess in future studies.
Of importance, our data indicate that measures of trunk fat (both percent trunk fat and trunk to extremity fat ratio) are deleterious to BMD in AA more than in EA. These findings suggest that menstrual status may impact the site-specific effects of fat mass on bone density, with estrogen deficiency in AA unmasking the inverse association between trunk fat and bone. Estrogen is known to inhibit osteoclastic activity by inhibiting secretion of proinflammatory cytokines (35
), and one may speculate that in the absence of estrogen, there is an increased secretion of these proinflammatory cytokines from visceral fat, contributing to impaired bone metabolism in AA, but not EA. However, even after controlling for estradiol levels, percent trunk fat was negatively associated with many bone density measures, suggesting that percent trunk fat may have an impact on bone that may `trump' the effects of estrogen. Of note, because we obtained estradiol levels in the early follicular phase of the cycle in eumenorrheic athletes when estrogen levels are the lowest, these levels may not reflect overall estrogen status. Felding and colleagues have indicated that there may also be a “threshold” level of estrogen that is too low to support menses, but high enough to support some anabolic effects of exercise on bone (36
). Low bone density in our AA group suggests that these girls had estrogen levels that were even lower than this `threshold' level, and as a consequence, anabolic effects of exercise on bone were lost.
Regardless of the mechanisms that underlie the impact of regional body composition on BMD, our study clearly illustrates the importance of lean and fat mass in athletes and further elucidates the mechanism whereby amenorrhea has strong deleterious effects on bone. Amenorrhea may simply indicate overtraining and poor energy balance, both associated with decreased gonadal function and increased cortisol and cytokine levels. Amenorrhea is certainly not a healthy response to exercise and can have long-term consequences on bone health if not addressed. Our study highlights the necessity of understanding the mechanisms underlying exercise-induced amenorrhea and methods of preventing or reversing both the menstrual irregularity and consequent bone loss.
There were certain limitations of our study, including the size of the study cohort. Replication of the study with a greater sample size could yield more significant relationships between site-specific measures of body composition and BMD. Furthermore, although DXA measures are validated surrogate markers for body composition, and are fast, cost-effective, and emit much less radiation than computed tomography, MRI or CT measurements are the most accurate and precise methods of assessing body composition. Although we did not assess visceral fat using CT or MRI, studies have indicated that certain DXA measures of body composition, such as total fat, are good surrogates for subcutaneous fat, while estimates of percent trunk fat and trunk to extremity fat ratio are good surrogates for visceral fat. An additional limitation is that our study was cross-sectional and does not establish causality. To more accurately assess the interrelationship between site-specific body composition, weight-bearing exercise and bone density in the adolescent athlete, a longitudinal study over several years (menarche to adulthood) would yield more confirmatory results. Importantly, our study provides preliminary data indicating the need and rationale for such future studies.
Our study illustrates that amenorrhea may sometimes override the bone anabolic effects of lean mass on mechanical loading, and may also unmask the deleterious impact of visceral fat on bone. Further research is necessary to elucidate the mechanisms underlying the impact of amenorrhea on muscle, fat, bone, and overall health. For now, education of both athletes and coaches is necessary to underscore awareness of the female athlete triad and its important health consequences.