In this nationally representative sample study, we found that SCre level within the normal range was independently associated with total BMD among adolescents aged 12–19 years. Additionally, this association remained positive in each subgroup stratified by age, gender, or race, and was more prominent in boys than in girls in adolescents aged 12–15 years.
Muscle is the largest organ in the body that accounts for 40% of body mass. Muscles grow larger and stronger from birth and start to lose its mass from 25 years of age. The loss in muscle mass and consequently its strength results in sarcopenia. Several evidences suggest that individuals with sarcopenia had lower BMD and a higher risk of osteoporosis[15–17]. SCre concentration may be affected by changes in muscle mass. However, evidence regarding the correlation between SCre and bone health is limited.
To evaluate the correlation of SCre with BMD among older adult with normal renal function, Huh et al. conducted a cross-sectional study using the Fourth Korea NHANES data. Their findings provided the first clinical evidence that low SCre level was independently associated with low BMD. Moreover, their data showed that the positive association between SCre and BMD was more prominent in men than in women. In our study, SCre levels differed by gender. It might be explained by the fact that boys have higher muscle mass than girls. However, after controlling for potential confounding factors, SCre level within the normal range was positively associated with total BMD in adolescents in each subgroup stratified by age, gender, or race. Furthermore, this positive association was more prominent in boys than in girls in adolescents aged 12–15 years. These findings were consistent with the previous study focusing on older adults.
It is widely accepted that the increase in peak bone mass achieved during adolescence is effective in preventing osteoporosis and osteoporosis-associated fractures. Creatine has been a popular dietary supplement choice of adolescents, and no study has observed any gastro-intestinal discomforts or changes in markers of clinical health and safety following creatine supplement use periods. Thus, adequate creatine supplementation may be a new strategy for adolescents with low SCre.
By our knowledge, this is the first study that evaluated the association between SCre and BMD in adolescents. Additionally, this nationally representative sample makes our conclusions persuasive and highly relevant to the whole population. However, several weaknesses of our study must be acknowledged. First, due to the cross-sectional nature of NHANES data, it is incapable of indicating the causal association between SCre and BMD. Therefore, a longitudinal follow-up study is required to clarificate the role of creatinine metabolism on bone health. Second, we excluded subjects with abnormal SCre levels, because renal dysfunction may influence BMD[21, 22]. Therefore, our conclusions cannot be used for this special population. Third, other potential confounding factors not included in this study may cause some bias. For example, differences in gender and developmental age during pubertal development is a potential confounding factor in the present study. Hence, we conducted subgroup analyses stratified by age and gender to confirm the results.
In conclusion, our findings indicate that higher SCre levels within the normal range in adolescents aged 12–19 years were associated with higher total BMDs, suggesting that SCre may be a candidate biomarker for bone health in adolescents. It is our hope that this study will stimulate future multidisciplinary research on the effect of creatine and creatinine metabolism on bone health in adolescents.