Hypotheses: Values of serum markers related to bone quality are abnormal in young female ballet dancers. Methods: In 13 elite Japanese female ballet dancers (average age, 22 years), markers related to bone quality were investigated. These included: serum homocystein (HC), a marker of increased oxidative stress; pentosidine (Pent), a marker of glycation- or oxidation-induced non-enzymatic cross-links; markers of bone metabolism (bone alkaline phosphatase, BAP; tartrate-resistant acid phosphatase 5b, TRAP5b) and bone mineral density (BMD). It was determined whether there is a relationship between bone quality markers’ levels are related to amenorrhea and/or fatigue fractures. Results: Two dancers had fatigue fractures and 3 had a history of secondary amenorrhea. The average BMD was 1.305 ± 0.12 (g/cm 2), in all these cases the Z-score was higher than -1.0. Although the serum levels of BAP, TRAP5b, and HC were normal in all examined dancers, in 2 out of 3 dancers with a history of secondary amenorrhea, pentosidine serum levels were increased. No relationship between bone quality markers’ levels and fatigue fractures was found. Conclusion: Latent deterioration of bone quality may occur in female athletes with secondary amenorrhea and otherwise normal BMD and calcium metabolism markers.
The position stand, introduced by the American College of Sports Medicine (ACSM), defined the female athlete triad (FAT) as low energy availability, amenorrhea and osteoporosis [
The purpose of this study was to evaluate bone quality in elite female ballet dancers by measuring serum HC and Pent levels as well as BMD and bone metabolism markers, and to determine whether these markers show any relationship with amenorrhea and/or fatigue fractures.
Inclusion criteria were the dancers 1): their age was 20 years old or over, 2): their training experience was 10 years or more, and 3): their training frequency was more than five days in a week. Out of 20 top-leveled female ballet dancers of the Ochanomizu University in Tokyo, Japan, who filled the above criteria, 13 dancers (mean and SD; age: 21.8 ± 2.0 years; body mass: 49 ± 6.3 kg; height: 160.7 ± 6.4 cm and BMI 18.8 ± 1.2 kg∙m−2) with an average 15.8 years of training experience agreed to participate in this study. All subjects signed a written informed consent. The ethic committees of Jikei University (No. 23-026) and Ochanomizu University (No. 23-3) approved the study design.
The dancers were asked to fill a health status questionnaire, which included questions on history of fatigue fractures, menstrual history and cycle characteristics, history of other diseases and drug use, including oral contraceptive agents. A regular cycle was defined as menstrual periods occurring every 21 to 35 days. Primary amenorrhea was defined as absence of menarche by the age of 15 years and secondary amenorrhea as cessation of menses for three or more consecutive cycles after the menarche onset. Oligomenorrhea was defined as menstrual bleeding occurring at intervals longer than 35 days [
BMD of the lumbar spine (L1?L4) was examined by dual-energy X-ray absorptiometry (DXA) (GE Lunar Prodigy densitometer, Version 10.51; Madison, Wisconsin) and body composition was also assessed. The daily coefficient of variation of the calibration phantom over a 6-month period was 0.16%. The International Society for Clinical Densitometry (ISCD), World Health Organization (WHO), and ACSM classification systems were used to define low BMD based on Z-scores.
Blood samples were obtained by venipuncture in the afternoon and the following serum parameters were measured: 1) serum bone metabolic markers: bone alkaline phosphatase (BAP) and tartrate-resistant acid phosphatase 5b (TRAP5b); 2) bone quality-related markers: HC and Pent; 3) thyroid-stimulating hormone (TSH), intact parathyroid hormone (iPTH) and adrenocorticotropic hormone (ACTH) to exclude endocrinologic disturbances potentially involved in regulation of calcium metabolism. All blood examinations were carried out at the SRL laboratory (Tokyo, Japan) accordingly with the previously reported methods [
Database construction and statistical analyses were performed using SPSS for Windows (version 19, IBM Corp). Continuous variables were expressed as mean ± SD. Pearson product moment correlation coefficients were computed to determine a relationship between BMD and Pent. Statistical significance was set at p ≤ 0.05.
Two ballet dancers had a history of fatigue fracture: one developed bilateral pars-interarticularis fracture of the 4th lumbar spine (spondylolysis) (case No. 4) and the other suffered from a tibial fracture (case No. 9). They occurred 8 and 14 years before commencement of the study, respectively, and were conservatively treated (
The onset age of menarche was from 11 to 15 years, 12.8 years in average. Three subjects had a history of secondary amenorrhea (cases No. 3, 6, 10); in these cases, the age at menarche cessation was 19, 18 and 17 years, respectively. The duration of amenorrhea was 2 years in all subjects. In case 6, the dancer continuously suffered from amenorrhea until the time of present study. Overall, 4
Case No. | Age (years old) | Height (cm) | Weight (kg) | BMI** (kg/m2) | Training Experience (years) | Age at first menarche |
---|---|---|---|---|---|---|
1 | 21 | 164 | 53 | 19.7 | 14 | 13 |
2 | 23 | 160 | 47 | 18.4 | 15 | 12 |
3 | 21 | 162 | 54 | 20.5 | 18 | 14 |
4 | 22 | 158 | 47 | 18.9 | 13 | 14 |
5 | 24 | 159 | 46 | 18.1 | 19 | 12 |
6 | 20 | 149 | 40 | 17.8 | 16 | 12 |
7 | 20 | 152 | 42 | 18.1 | 10 | 11 |
8 | 20 | 163 | 48 | 18 | 16 | 13 |
9 | 27 | 169 | 51 | 17.8 | 24 | 15 |
10 | 21 | 158 | 49 | 19.5 | 13 | 11 |
11 | 21 | 174 | 65 | 21.5 | 16 | 14 |
12 | 21 | 161 | 50 | 19.2 | 15 | 11 |
13 | 22 | 161 | 45 | 17.3 | 17 | 15 |
Mean | 21.8 | 160.8 | 49 | 18.8 | 15.8 | 12.8 |
S.D* | 2 | 6.4 | 6.2 | 1.2 | 3.4 | 1.5 |
* Standard Deviation ** Body Mass Index.
Case No. | Fatigue fracture (location) | Secondary amenorrhea | Period of amenorrhea (years of age) | BMD** (g/cm2) | Z-score |
---|---|---|---|---|---|
1 | ― | no | ― | 1.397 | 1.4 |
2 | ― | no | ― | 1.232 | 1.4 |
3 | ― | yes | 19~21 | 1.402 | 1.9 |
4 | 4th lumbar | no | ― | 1.238 | 1.1 |
5 | ― | no | ― | 1.302 | 1.6 |
6 | ― | yes | 18~20 | 1.064 | 0 |
7 | ― | no | ― | 1.288 | 1.7 |
8 | ― | no | ― | 1.226 | 0.9 |
9 | Tibia | no | ― | 1.416 | 2.2 |
10 | ― | yes | 17~19 | 1.36 | 1.9 |
11 | ― | no | ― | 1.356 | 0.9 |
12 | ― | no | ― | 1.518 | 3.1 |
13 | ― | no | ― | 1.164 | 0.5 |
Mean | 1.305 | 1.43 | |||
S.D* | 0.121 | 0.79 |
* Standard Deviation **Bone mineral density.
subjects considered their menstrual cycles as irregular in the questionnaire (3 cases with amenorrhea and one case without, case No. 12).
BMD ranged from 1.064 to 1.518 g/cm2 and averaged 1.305 ± 0.121 g/cm2. T-score was from −0.6 to 3.1 (1.34 in average), and Z-score was from 0 to 3.1 (1.43 in average), in all dancers the scores were higher than −2.5 and −1.0, for T- and Z-score, respectively.
In all subjects, BAP, TRAP5b, TSH, iPTH and ACTH values were within normal limits. Although HC levels in all subjects were normal, in 2 dancers (cases No. 6, 10) the levels of Pent were abnormally increased. Both two subjects also had a history of secondary amenorrhea (
(BAP: bone alkaline phosphatase, TRAP5b: tartrate-resistant acid phosphatase 5b, HC: homocystein, Pent: pentosidine, TSH: thyroid-stimulating hormone, iPTH: intact parathyroid hormone, ACTH: adrenocorticotropic hormone).
Case No. | BAP (μg/l) | TRAP5b (mU/dl) | HC (nmol/ml) | Pent (μg/ml) | TSH (μIU/m) | iPTH (pg/ml) | ACTH (pg/ml) |
---|---|---|---|---|---|---|---|
1 | 11.8 | 183 | 6.0 | 0.0186 | 1.46 | 42 | 14.4 |
2 | 19.3 | 163 | 7.9 | 0.0332 | 1.56 | 23 | 10.3 |
3 | 12.9 | 175 | 8.0 | 0.0308 | 3.61 | 26 | 19.3 |
4 | 12.5 | 279 | 8.3 | 0.0407 | 1.71 | 30 | 12.7 |
5 | 16.9 | 133 | 6.0 | 0.041 | 1.26 | 27 | 16.4 |
6 | 12.2 | 167 | 5.5 | 0.0526* | 1.59 | 22 | 9.9 |
7 | 10.2 | 150 | 5.5 | 0.0268 | 3.22 | 20 | 10.3 |
8 | 15.5 | 262 | 6.8 | 0.0361 | 1.4 | 15 | 12.7 |
9 | 7.3 | 159 | 9.5 | 0.0359 | 1.88 | 37 | 25.5 |
10 | 12.1 | 159 | 5.9 | 0.0522* | 0.97 | 28 | 13.7 |
11 | 9.7 | 274 | 7.4 | 0.0381 | 1.07 | 36 | 14.9 |
12 | 14.2 | 159 | 7.3 | 0.0248 | 0.74 | 32 | 22 |
13 | 15.2 | 291 | 5.1 | 0.0223 | 1.27 | 32 | 15.4 |
Normal | 2.9~ | 120~ | 3.7~ | 0.00915~ | 0.34~ | 10~ | 7.2~ |
range | 20.9 | 420 | 13.5 | 0.0431 | 4.04 | 65 | 63.3 |
*abnormally high leve.
Although epidemiologic data relating BMD to fractures in adolescents and premenopausal women are lacking, athletes doing weight-bearing sports usually have 5% - 15% higher BMDs than non-athletes [
BMD and menstrual cycle relationship was also addressed. Warren et al. [
Furthermore, an association between low BMD and stress fractures has been reported in female athletes including dancers [
Shiraki et al. divided bone fragility into three types based on BMD and bone quality involvement in postmenopausal population: 1) low BMD with normal bone quality; 2) bone quality degradation with normal BMD, and 3) low BMD with bone quality degradation, and investigated the risk of the fractures compared to the women who had normal BMD and bone quality. They concluded that fracture risk ratio was 3.6, 1.5, and 7.2 times higher, respectively [
Although bone quality is a dependent factor and plays an important role in bone strength in postmenopausal population, little attention has been paid to bone quality in young female athletes and there has been only one report available in the literature addressing this issue. Wakamatsu et al. reported that HC and Pent were not significantly different between lacrosse players who had experienced stress fracture and those who had not [
The present study demonstrated that in 2 out of 13 dancers, the levels of pentosidine were increased notwithstanding normal stress oxidative markers and bone metabolism markers including BMD. These subjects were also the two out of 3 subjects with secondary amenorrhea. It has been reported that Pent increases due to several factors such as aging, estrogen impairment, increased oxidative stress, diabetes and zero gravity [
The present study has several limitations. It was a cross-sectional study, not case control or prospective study, and the number of subjects was small. The reasons why in 2 subjects pentosidine levels were high without decreased BMD remain unknown. We consider two potential explanations. First, the subjects with abnormally high levels of Pent also had low BMD due to secondary amenorrhea, but Pent levels had not yet recovered even BMD values normalized after re-start of menarche. This could have meant that bone quality recovery time is longer than that of BMD even after re-start of menstrual cycle. Second, high pentosidine levels were caused by secondary amenorrhea without any influence on BMD.
Timing of blood testing during menstrual cycle in the two subjects with higher pentosidine levels was not standardized. This is another limitation of the study, because there is evidence for cycle-related changes in other bone markers along phases of menstrual cycle [
Notwithstanding the limitations, our study indicates that latent deterioration of bone quality can develop in female athletes who have experienced secondary amenorrhea but present with otherwise normal BMD and other calcium metabolic markers. Although we did not find any correlation between pentosidine levels and fatigue fractures, further prospective studies on the relationship between bone quality and stress fractures are necessary.
The authors thank the ballet dancers for participating in this study.
The authors declare that there is no conflict of interests regarding the publication of this article.
Funasaki, H., Saito, M., Kuno-Mizumura, M., Hayashi, H. and Marumo, K. (2017) Bone Quality in Female Ballet Dancers: A Possible Determinant of Bone Health. Open Journal of Orthopedics, 7, 284-293. https://doi.org/10.4236/ojo.2017.79028