Prevalence and risk factors associated with low bone mineral density in Asian adolescents with anorexia nervosa and atypical anorexia nervosa
Corresponding Author
Courtney Davis MD
Adolescent Medicine Service, KK Women's and Children's Hospital, Singapore, Singapore
SingHealth Duke-NUS Paediatric Academic Clinical Programme, Singapore, Singapore
Correspondence
Courtney Davis, Adolescent Medicine Service, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore 229899, Singapore.
Email: [email protected]
Contribution: Conceptualization, Formal analysis, Investigation, Methodology, Supervision, Writing - original draft, Writing - review & editing
Search for more papers by this authorHannah Marian Mei En Lie MBBS
Lee Kong Chian School of Medicine, Novena Campus, Clinical Sciences Building, Singapore, Singapore
Contribution: Conceptualization, Data curation, Formal analysis, Methodology, Writing - original draft
Search for more papers by this authorRashida Farhad Vasanwala MD
SingHealth Duke-NUS Paediatric Academic Clinical Programme, Singapore, Singapore
Endocrinology Service, KK Women's and Children's Hospital, Singapore, Singapore
Contribution: Conceptualization, Writing - review & editing
Search for more papers by this authorJuliet Sher Kit Tan MD
Adolescent Medicine Service, KK Women's and Children's Hospital, Singapore, Singapore
SingHealth Duke-NUS Paediatric Academic Clinical Programme, Singapore, Singapore
Contribution: Writing - review & editing
Search for more papers by this authorJean Yin Oh MB, BCh, BAO
Adolescent Medicine Service, KK Women's and Children's Hospital, Singapore, Singapore
SingHealth Duke-NUS Paediatric Academic Clinical Programme, Singapore, Singapore
Contribution: Writing - review & editing
Search for more papers by this authorKumudhini Rajasegaran MB, Bch, BAO
Adolescent Medicine Service, KK Women's and Children's Hospital, Singapore, Singapore
SingHealth Duke-NUS Paediatric Academic Clinical Programme, Singapore, Singapore
Contribution: Writing - review & editing
Search for more papers by this authorChu Shan Elaine Chew MBBS
Adolescent Medicine Service, KK Women's and Children's Hospital, Singapore, Singapore
SingHealth Duke-NUS Paediatric Academic Clinical Programme, Singapore, Singapore
Contribution: Conceptualization, Formal analysis, Methodology, Writing - review & editing
Search for more papers by this authorCorresponding Author
Courtney Davis MD
Adolescent Medicine Service, KK Women's and Children's Hospital, Singapore, Singapore
SingHealth Duke-NUS Paediatric Academic Clinical Programme, Singapore, Singapore
Correspondence
Courtney Davis, Adolescent Medicine Service, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore 229899, Singapore.
Email: [email protected]
Contribution: Conceptualization, Formal analysis, Investigation, Methodology, Supervision, Writing - original draft, Writing - review & editing
Search for more papers by this authorHannah Marian Mei En Lie MBBS
Lee Kong Chian School of Medicine, Novena Campus, Clinical Sciences Building, Singapore, Singapore
Contribution: Conceptualization, Data curation, Formal analysis, Methodology, Writing - original draft
Search for more papers by this authorRashida Farhad Vasanwala MD
SingHealth Duke-NUS Paediatric Academic Clinical Programme, Singapore, Singapore
Endocrinology Service, KK Women's and Children's Hospital, Singapore, Singapore
Contribution: Conceptualization, Writing - review & editing
Search for more papers by this authorJuliet Sher Kit Tan MD
Adolescent Medicine Service, KK Women's and Children's Hospital, Singapore, Singapore
SingHealth Duke-NUS Paediatric Academic Clinical Programme, Singapore, Singapore
Contribution: Writing - review & editing
Search for more papers by this authorJean Yin Oh MB, BCh, BAO
Adolescent Medicine Service, KK Women's and Children's Hospital, Singapore, Singapore
SingHealth Duke-NUS Paediatric Academic Clinical Programme, Singapore, Singapore
Contribution: Writing - review & editing
Search for more papers by this authorKumudhini Rajasegaran MB, Bch, BAO
Adolescent Medicine Service, KK Women's and Children's Hospital, Singapore, Singapore
SingHealth Duke-NUS Paediatric Academic Clinical Programme, Singapore, Singapore
Contribution: Writing - review & editing
Search for more papers by this authorChu Shan Elaine Chew MBBS
Adolescent Medicine Service, KK Women's and Children's Hospital, Singapore, Singapore
SingHealth Duke-NUS Paediatric Academic Clinical Programme, Singapore, Singapore
Contribution: Conceptualization, Formal analysis, Methodology, Writing - review & editing
Search for more papers by this authorCourtney Davis and Hannah Marian Mei En Lie share the first authorship.
Abstract
Objective
This retrospective study aimed to evaluate the prevalence and risk factors for low bone mineral density (BMD) at diagnosis in Asian adolescent females with anorexia nervosa (AN) and atypical AN.
Method
We analyzed the BMD results for 213 patients between 10 and 18 years of age, with AN and atypical AN receiving care at a pediatric hospital in Singapore. We used linear regression analyses to determine if type of eating disorder, premorbid weight, and duration of amenorrhea were risk factors for low BMD. For a subset of patients with repeat BMD evaluation, we used paired t-tests to assess the impact of weight or menstrual restoration on the change in BMD.
Results
The prevalence of BMD height-for-age Z-scores <−2 at presentation was higher in patients with AN (13.0%) than atypical AN (2.3%) (p = .034). In multivariate regression, a diagnosis of atypical AN was protective against low BMD at the lumbar spine (B = 0.394, p = .009) and total body less head (B = 0.774, p = .010). Duration of amenorrhea was not associated with BMD across all sites. For those with repeat BMD measures, there was significantly less deterioration in the BMD Z-scores for patients with weight or menstrual restoration (R = −0.22 ± 0.59, NR = −0.69 ± 0.43, p = .029).
Conclusions
Duration of amenorrhea was not associated with BMD in this sample. A diagnosis of AN was correlated with lower BMD than atypical AN. Further research is needed to better understand the relationship between amenorrhea, weight status, and bone health in Asian adolescents with eating disorders.
Public Significance
In this sample, 13% of Asian adolescents with AN and 2.3% of Asian adolescents with atypical AN have low BMD. In our study population, duration of amenorrhea was not correlated with BMD. Among adolescents with AN, a history of being underweight at the highest pre-morbid BMI, is correlated with low BMD. It is important for physicians to take a thorough weight history in evaluating bone health in this population.
CONFLICT OF INTEREST STATEMENT
All authors have no potential sources of conflict of interest.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
REFERENCES
- American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders ( 5th ed.). American Psychiatric Association Publishing.
10.1176/appi.books.9780890425596 Google Scholar
- Barrett-Connor, E., Siris, E. S., Wehren, L. E., Miller, P. D., Abbott, T. A., Berger, M. L., Santora, A. C., & Sherwood, L. M. (2005). Osteoporosis and fracture risk in women of different ethnic groups. Journal of Bone and Mineral Research, 20(2), 185–194. https://doi.org/10.1359/JBMR.041007
- Chew, C. S. E., Kelly, S., Baeg, A., Oh, J. Y., Rajasegaran, K., & Davis, C. (2021). First presentation of restrictive early onset eating disorders in Asian children. The International Journal of Eating Disorders, 54(1), 81–87. https://doi.org/10.1002/eat.23274
- Chew, C. S. E., Kelly, S., Tay, E. E., Baeg, A., Khaider, K. B., Oh, J. Y., Rajasegaran, K., Saffari, S. E., & Davis, C. (2021). Implementation of family-based treatment for Asian adolescents with anorexia nervosa: A consecutive cohort examination of outcomes. The International Journal of Eating Disorders, 54(1), 107–116. https://doi.org/10.1002/eat.23429
- Cong, E., & Walker, M. D. (2014). The Chinese skeleton: Insights into microstructure that help to explain the epidemiology of fracture. Bone Research, 2, 14009. https://doi.org/10.1038/boneres.2014.9
- Davis, C., Hong, W. J. N., Zhang, S. L., Quek, W. E. G., Lim, J. K. E., Oh, J. Y., Rajasegaran, K., & Chew, C. S. E. (2021). Outcomes of a higher calorie inpatient refeeding protocol in Asian adolescents with anorexia nervosa. The International Journal of Eating Disorders, 54(1), 95–101. https://doi.org/10.1002/eat.23403
- Deng, K. L., Yang, W. Y., Hou, J. L., Li, H., Feng, H., & Xiao, S. M. (2021). Association between body composition and bone mineral density in children and adolescents: A systematic review and meta-analysis. International Journal of Environmental Research and Public Health, 18(22), 12126. https://doi.org/10.3390/ijerph182212126
- Drabkin, A., Rothman, M. S., Wassenaar, E., Mascolo, M., & Mehler, P. S. (2017). Assessment and clinical management of bone disease in adults with eating disorders: A review. Journal of Eating Disorders, 5, 42. https://doi.org/10.1186/s40337-017-0172-0
- Faje, A. T., Fazeli, P. K., Miller, K. K., Katzman, D. K., Ebrahimi, S., Lee, H., Mendes, N., Snelgrove, D., Meenaghan, E., Misra, M., & Klibanski, A. (2014). Fracture risk and areal bone mineral density in adolescent females with anorexia nervosa. The International Journal of Eating Disorders, 47(5), 458–466. https://doi.org/10.1002/eat.22248
- Finkelstein, J. S., Sowers, M., Greendale, G. A., Lee, M. L., Neer, R. M., Cauley, J. A., & Ettinger, B. (2002). Ethnic variation in bone density in premenopausal and early perimenopausal women: Effects of anthropometric and lifestyle factors. The Journal of Clinical Endocrinology and Metabolism, 87(7), 3057–3067. https://doi.org/10.1210/jcem.87.7.8654
- Franzoni, E., Ciccarese, F., Di Pietro, E., Facchini, G., Moscano, F., Iero, L., Monaldi, A., Battista, G., & Bazzocchi, A. (2014). Follow-up of bone mineral density and body composition in adolescents with restrictive anorexia nervosa: Role of dual-energy X-ray absorptiometry. European Journal of Clinical Nutrition, 68(2), 247–252. https://doi.org/10.1038/ejcn.2013.254
- Gatti, D., El Ghoch, M., Viapiana, O., Ruocco, A., Chignola, E., Rossini, M., Giollo, A., Idolazzi, L., Adami, S., & Dalle Grave, R. (2015). Strong relationship between vitamin D status and bone mineral density in anorexia nervosa. Bone, 78, 212–215. https://doi.org/10.1016/j.bone.2015.05.014
- Giollo, A., Idolazzi, L., Caimmi, C., Fassio, A., Bertoldo, F., Dalle Grave, R., El Ghoch, M., Calugi, S., Bazzani, P. V., Viapiana, O., Rossini, M., & Gatti, D. (2017). Vitamin D levels strongly influence bone mineral density and bone turnover markers during weight gain in female patients with anorexia nervosa. The International Journal of Eating Disorders, 50(9), 1041–1049. https://doi.org/10.1002/eat.22731
- Golden, N. H., Katzman, D. K., Sawyer, S. M., Ornstein, R. M., Rome, E. S., Garber, A. K., Kohn, M., & Kreipe, R. E. (2015). Update on the medical management of eating disorders in adolescents. Journal of Adolescent Health, 56(4), 370–375. https://doi.org/10.1016/j.jadohealth.2014.11.020
- Gordon, C. M., Leonard, M. B., & Zemel, B. S. (2014). 2013 Pediatric position development conference: Executive summary and reflections. Journal of Clinical Densitometry, 17(2), 219–224. https://doi.org/10.1016/j.jocd.2014.01.007
- Halvorsen, I., Platou, D., & Hoiseth, A. (2012). Bone mass eight years after treatment for adolescent-onset anorexia nervosa. European Eating Disorders Review, 20(5), 386–392. https://doi.org/10.1002/erv.2179
- Harrop, E. N., Mensinger, J. L., Moore, M., & Lindhorst, T. (2021). Restrictive eating disorders in higher weight persons: A systematic review of atypical anorexia nervosa prevalence and consecutive admission literature. International Journal of Eating Disorders., 54, 1328–1357. https://doi.org/10.1002/eat.23519
- Kim, A., Baek, S., Park, S., & Shin, J. (2020). Bone mineral density of femur and lumbar and the relation between fat mass and lean mass of adolescents: Based on Korea National Health and Nutrition Examination Survey (KNHNES) from 2008 to 2011. International Journal of Environmental Research and Public Health, 17(12), 4471. https://doi.org/10.3390/ijerph17124471
- Kouda, K., Ohara, K., Nakamura, H., Fujita, Y., Jaalkhorol, M., & Iki, M. (2018). Fat mass is positively associated with bone mass acquisition in children with small or normal lean mass: A three-year follow-up study. Bone, 107, 222–227. https://doi.org/10.1016/j.bone.2017.12.003
- Lee, H., Lee, E., Pathy, P., & Chan, Y. (2005). Anorexia nervosa in Singapore: An eight-year retrospective study. Singapore Medical Journal, 46(6), 275–281.
- Lopes, M. P., Robinson, L., Stubbs, B., Dos Santos Alvarenga, M., Araujo Martini, L., Campbell, I. C., & Schmidt, U. (2022). Associations between bone mineral density, body composition and amenorrhoea in females with eating disorders: A systematic review and meta-analysis. Journal of Eating Disorders, 10(1), 173. https://doi.org/10.1186/s40337-022-00694-8
- Messinis, I. E. (2006). From menarche to regular menstruation: Endocrinological background. Annals of the new York Academy of Sciences, 1092, 49–56. https://doi.org/10.1196/annals.1365.004
- Ministry of Health (2015a). Singapore Government Health Promotion Board. (2002). Percentile of body mass index-for-age anthropometric study on school age children in Singapore. Retrieved from https://www.healthhub.sg/sites/assets/Assets/PDFs/HPB/Children/HPB%20-%20Boys-new%20(Live%20Healthy%20745).pdf
- Ministry of Health (2015b). Singapore Government Health Promotion Board. (2002). Percentile of body mass index-for-age anthropometric study on school age children in Singapore. Retrieved from https://www.healthhub.sg/sites/assets/Assets/PDFs/HPB/Children/HPB%20-%20Girls-new%20(Live%20Healthy%20745).pdf
- Misra, M., Aggarwal, A., Miller, K. K., Almazan, C., Worley, M., Soyka, L. A., Herzog, D. B., & Klibanski, A. (2004). Effects of anorexia nervosa on clinical, hematologic, biochemical, and bone density parameters in community-dwelling adolescent girls. Pediatrics, 114(6), 1574–1583. https://doi.org/10.1542/peds.2004-0540
- Misra, M., & Klibanski, A. (2011). Bone health in anorexia nervosa. Current Opinion in Endocrinology, Diabetes, and Obesity, 18(6), 376–382. https://doi.org/10.1097/MED.0b013e32834b4bdc
- Misra, M., & Klibanski, A. (2014). Endocrine consequences of anorexia nervosa. The Lancet Diabetes & Endocrinology, 2(7), 581–592. https://doi.org/10.1016/s2213-8587(13)70180-3
- Misra, M., Prabhakaran, R., Miller, K. K., Goldstein, M. A., Mickley, D., Clauss, L., Lockhart, P., Cord, J., Herzog, D. B., Katzman, D. K., & Klibanski, A. (2008). Weight gain and restoration of menses as predictors of bone mineral density change in adolescent girls with anorexia Nervosa-1. The Journal of Clinical Endocrinology & Metabolism, 93(4), 1231–1237. https://doi.org/10.1210/jc.2007-1434
- Nagata, J. M., Carlson, J. L., Golden, N. H., Long, J., Murray, S. B., & Peebles, R. (2019). Comparisons of bone density and body composition among adolescents with anorexia nervosa and atypical anorexia nervosa. The International Journal of Eating Disorders, 52(5), 591–596. https://doi.org/10.1002/eat.23048
- Nagata, J. M., Carlson, J. L., Golden, N. H., Murray, S. B., Long, J., Leonard, M. B., & Peebles, R. (2019). Associations between exercise, bone mineral density, and body composition in adolescents with anorexia nervosa. Eating and Weight Disorders, 24(5), 939–945. https://doi.org/10.1007/s40519-018-0521-2
- Ogden, C. L., & Flegal, K. M. (2010). Changes in terminology for childhood overweight and obesity. National Health Statistics Reports, (25), 1–5.
- Pehlivanturk-Kizilkan, M., Akgul, S., Derman, O., & Kanbur, N. (2021). Predictors of bone mineral density in adolescents with atypical anorexia nervosa. Journal of Bone and Mineral Metabolism, 39(4), 678–683. https://doi.org/10.1007/s00774-021-01211-8
- Pike, K. M., & Dunne, P. E. (2015). The rise of eating disorders in Asia: A review. Journal of Eating Disorders, 3, 33. https://doi.org/10.1186/s40337-015-0070-2
- Schorr, M., Thomas, J. J., Eddy, K. T., Dichtel, L. E., Lawson, E. A., Meenaghan, E., Lederfine Paskal, M., Fazeli, P. K., Faje, A. T., Misra, M., Klibanski, A., & Miller, K. K. (2017). Bone density, body composition, and psychopathology of anorexia nervosa spectrum disorders in DSM-IV vs DSM-5. The International Journal of Eating Disorders, 50(4), 343–351. https://doi.org/10.1002/eat.22603
- Society for Adolescent Health and Medicine. (2022). Medical management of restrictive eating disorders in adolescents and young adults. The Journal of Adolescent Health, 71(5), 648–654. https://doi.org/10.1016/j.jadohealth.2022.08.006
- Soyka, L. A., Misra, M., Frenchman, A., Miller, K. K., Grinspoon, S., Schoenfeld, D. A., & Klibanski, A. (2002). Abnormal bone mineral accrual in adolescent girls with anorexia nervosa. The Journal of Clinical Endocrinology and Metabolism, 87(9), 4177–4185. https://doi.org/10.1210/jc.2001-011889
- Sum, M., Zhu, T. Y., Zhou, B., Zhang, Z., Bilezikian, J. P., Guo, X. E., Qin, L., & Walker, M. (2019). Chinese women in both the United States and Hong Kong have cortical microstructural advantages and more trabecular plates compared with white women. JBMR Plus, 3(4), e10083. https://doi.org/10.1002/jbm4.10083
- Tanaka, K., Hisada, K., Unno, K., Iijima, M., Unno, A., Tokita, A., … Yamashiro, Y. (2007). Bone mineral density in children and adolescent girls with anorexia nervosa in Japan. Pediatrics International, 49(5), 637–640. https://doi.org/10.1111/j.1442-200X.2007.02469.x
- Thu, W. P. P., Logan, S. J. S., Cauley, J. A., Kramer, M. S., & Yong, E. L. (2019). Ethnic differences in bone mineral density among midlife women in a multi-ethnic southeast Asian cohort. Archives of Osteoporosis, 19(4), 80. https://doi.org/10.1007/s11657-019-0631-0
10.1007/s11657-019-0631-0 Google Scholar
- Tobias, J. H., Cook, D. G., Chambers, T. J., & Dalzell, N. (1994). A comparison of bone mineral density between Caucasian, Asian and Afro-Caribbean women. Clinical Science, 87(5), 587–591. https://doi.org/10.1042/cs0870587
- Vo, M., Accurso, E. C., Goldschmidt, A. B., & Le Grange, D. (2017). The impact of DSM-5 on eating disorder diagnoses. International Journal of Eating Disorders, 50(5), 578–581. https://doi.org/10.1002/eat.22628
- Weir, C. B., & Jan, A. (2021). BMI classification percentile and cut off points. In StatPearls. StatPearls Publishing LLC.
- Wong, S., Au, B., Lau, E., Lee, Y., Sham, A., & Lee, S. (2004). Osteoporosis in Chinese patients with anorexia nervosa. The International Journal of Eating Disorders, 36(1), 104–108. https://doi.org/10.1002/eat.20010
- Yong, E. L., Ganesan, G., Kramer, M. S., Logan, S., Lau, T. C., Cauley, J. A., & Tan, K. B. (2019). Hip fractures in Singapore: Ethnic differences and temporal trends in the new millennium. Osteoporosis International, 30(4), 879–886. https://doi.org/10.1007/s00198-019-04839-5
- Zemel, B. S., Kalkwarf, H. J., Gilsanz, V., Lappe, J. M., Oberfield, S., Shepherd, J. A., Frederick, M. M., Huang, X., Lu, M., Mahboubi, S., Hangartner, T., & Winer, K. K. (2011). Revised reference curves for bone mineral content and areal bone mineral density according to age and sex for black and non-black children: Results of the bone mineral density in childhood study. The Journal of Clinical Endocrinology & Metabolism, 96(10), 3160–3169. https://doi.org/10.1210/jc.2011-1111
- Zemel, B. S., Leonard, M. B., Kelly, A., Lappe, J. M., Gilsanz, V., Oberfield, S., Mahboubi, S., Shepherd, J. A., Hangartner, T. N., Frederick, M. M., Winer, K. K., & Kalkwarf, H. J. (2010). Height adjustment in assessing dual energy X-ray absorptiometry measurements of bone mass and density in children. The Journal of Clinical Endocrinology & Metabolism, 95(3), 1265–1273. https://doi.org/10.1210/jc.2009-2057
Citing Literature
