The Bone Mineral Density in Childhood Study (BMDCS) provides, for the first time, the longitudinal measurement of bone mass accrual in childhood, with linear growth, sexual and skeletal maturation, dietary intake, physical activity, and health history, in a large multi-center, multi-ethnic cohort of healthy children ages 5 to 20 years. This study, supported through the NICHD’s Pediatric Growth and Nutrition Branch (PGNB) (formerly the Endocrinology, Nutrition, and Growth (ENG) Branch), offered an unprecedented opportunity to identify predictors of the timing and magnitude of peak bone mass, a major determinant of osteoporosis in later adulthood.
BMDCS investigators have provided reference curves for bone accrual that are analogous to the Centers for Disease Control and Prevention (CDC) linear growth and weight gain curves for children and adolescents. The reference curves1, 2 generated by this carefully executed study provided the gold standard for normal bone accrual for generations to come. The study’s results enable practitioners to identify adverse effects chronic illness has on bone.
Additionally, the results have elucidated the effects that timing of pubertal onset has on bone density,3 the need for height adjustment to analyze dual-energy X-ray absorptiometry (DXA) scans in children,2 and the racial disparities in fracture rates in children.4 The NICHD will use the BMDCS data to further its research mission by enabling scientists to better understand and ultimately prevent osteopenia and osteoporosis. An online z-score calculator and height adjustment guidelines are provided at the BMDCS website.
The BMDCS Protocol
The BMDCS was conceived and solely sponsored by the NICHD with the primary goal of obtaining standard pediatric reference data for bone mineral density. Initial enrollment of 1,554 children ages 6 to 16 years at five clinical centers across the United States began in 2002 and ended in November 2003. This initial enrollment included an equal number of boys and girls and included diverse racial/ethnic groups. At enrollment, recruitment across the age groups was designed to provide larger sample sizes in both sexes at ages 6 and 10 and at age 14 in boys. There was a special focus on the recruitment of African American children because of the anticipated racial disparities in bone accrual.
In 2006, the study was extended for 3 years to recruit 5- and 19-year-olds, to provide an increased sample size at both tails of the reference curves and data for 5-year-olds and older ages (up to age 22). Enrollment into this extension phase began in July 2006 and was completed in November 2007, resulting in the addition of 460 children.
Five clinical centers (CCs), a core laboratory, and a Data Coordinating Center (DCC) participated in the study. The five CCs adhered to common procedures, which included dual-energy X-ray absorptiometry (DXA) to measure bone mineral density, bone age, anthropometric assessment (stadiometer height, weight, sitting height), physical exam by an endocrinologist to assess sexual maturation, and nutrition and exercise assessments. Throughout the study, the project officer and the DCC were responsible for the oversight of data collection and adherence to data quality standards.
The objective of this study was to establish normal values of bone mineral content (BMC) and BMD in 2,000 healthy American children, from 5 to 19 years old, by DXA. Measurement of bone density was performed by a Hologic densitometer. To study the correlation between DXA and computed tomography (CT), results in a subgroup of subjects were compared using quantitative CT (QCT) of the lumbar spine and peripheral quantitative CT (pqCT) of the forearm.
The careful implementation of the longitudinal protocol, with relatively few drop-outs in a large diverse cohort of healthy children, enabled the BMDCS investigators to collect valuable data on linear growth, the timing of puberty, bone age, nutrition, and exercise over a 6-year period. In 2010, a genome-wide association study (GWAS) was initiated to further study the BMDCS cohort and identify the underlying genetic determinants of peak bone mass and bone mineral accrual in childhood.
- Bone mineral accretion in childhood occurs at a slow and consistent pace, with a sharp increase during the pubertal growth spurt.
- Age at onset of puberty was a strong predictor of DXA bone measurements at skeletal maturity, independent of the length of puberty.
- BMD continues to rise into the third decade of life, even though an individual reaches adult height several years earlier.
- Men continue to accrue BMD for several years longer than women.
- Being white, male, and having a skeletal age of 10 to 14 years were the strongest risk factors for fracture.
- BMD measures show a high degree of tracking over time. Therefore, a child with low bone density will continue to have low bone density throughout childhood.
The study investigators created an online tool that health care providers can use to calculate BMD z-scores for their patients based upon the BMDCS reference data. Visit the Z-Score Calculator for more information on the tool.
Clinical Centers (Principal Investigator [PI])
- Children’s Hospital, Los Angeles (V. Gilsanz)
- Children’s Hospital Medical Center, Cincinnati (H. Kalkwarf)
- Children’s Hospital of Philadelphia (B. Zemel)
- Columbia University ( S. Oberfield)
- Creighton University (J. Lappe)
The NICHD project officer and chair of the BMDCS Steering Committee is Dr. Karen Winer. The Study’s Core Laboratory was at the University of California, San Francisco (PI: J. Shepherd). The DXA Quality Assurance Office was at Wright State University (PI: T. Handgartner). Clinical Trials and Surveys Corporation (C-TASC) served as the BMDCS Data Coordinating Center (DCC).
Wren, T. A. L., Liu, X., Pitukcheewanont, P., Gilsanz, V., & members of the BMDCS. (2005). Bone acquisition in healthy children and adolescents: comparison of dual-energy X-ray absorptiometry and computed tomography measures. Journal of Clinical Endocrinology & Metabolism, 90, 1925-1928.
- Kalkwarf, H. J., Zemel, B. S., Gilsanz, V., Lappe, J. M., Horlick, M., Oberfield, S., et al. (2007). The Bone Mineral Density in Childhood Study (BMDCS): bone mineral content and density according to age, sex, and race. Journal of Clinical Endocrinology & Metabolism, 92, 2087-2099. [top]
- Zemel, B. S., Kalkwarf, H. J., Gilsanz, V., Lappe, J. M., Oberfield, S., Shepherd, J. A., et al. (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 BMDCS. Journal of Clinical Endocrinology & Metabolism, 96, 3160-3169. [top]
- Gilsanz, V., Chalfant, J., Kalkwarf, H., Zemel, B., Lappe, J., Oberfield, S., et al. (2011). Age at onset of puberty predicts bone mass in young adulthood. Journal of Pediatrics, 158, 100-105, 5 e1-2. [top]
- Wren, T. A., Shepherd, J. A., Kalkwarf, H. J., Zemel, B. S., Lappe, J. M., Oberfield. S, et al. (In press). Racial disparity in fracture risk between white and non-white children. Journal of Pediatrics. [top]
Zemel, B. S., Leonard, M. B., Kelly, A., Lappe, J. M., Gilsanz, V., Oberfield, S, et al. (2010). Height adjustment in assessing dual energy x-ray absorptiometry measurements of bone mass and density in children. Journal of Clinical Endocrinology & Metabolism, 95, 1265-1273.
Kalkwarf, H., Gilsanz, V., Lappe, J. M., Oberfield, S., Shepherd, J. A., Hangartner, T. N., et al. (2010). Tracking of bone mass and density during childhood and adolescence. Journal of Clinical Endocrinology & Metabolism, 95, 1690-1698.
Short, D. F., Zemel, B. S., Gilsanz, V., Kalkwarf, H. J., Lappe, J. M., Mahboubi, S., et al. (2011). Fitting of bone mineral density with consideration of anthropometric parameters. Osteoporosis International, 22, 1047-1057.
Shepherd, J. A., Wang, L., Fan, B., Gilsanz, V., Kalkwarf, H. J., Lappe, J., et al. (2011). Optimal monitoring time interval between DXA measures in children. Journal of Bone Mineral Research, 26, 2745-2752.