The BMDCS is a multi-center, longitudinal study of bone accrual in healthy children and adolescents that was performed at 5 clinical centers in the United States. Detailed information about the study participants, inclusion/exclusion criteria, and study procedures have been published (2,5). The study provides the longitudinal measurement of bone mass, linear growth, sexual and skeletal maturation, dietary intake, physical activity, and health history. 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 provided reference curves for bone accrual and linear growth velocity that are analogous to the Centers for Disease Control and Prevention (CDC) linear growth and weight gain curves for children and adolescents. The reference curves (1,2) 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 and linear growth (5), the need for height adjustment to analyze dual-energy X-ray absorptiometry (DXA) scans in children,(1) and the racial disparities in fracture rates in children (7). The NICHD is using 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 (QDR4500/Delphi/Discovery models) following standardized procedures and analyzed centrally. 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).
- Zemel BS, Leonard MB, Kelly A, Lappe JM, Gilsanz V, Oberfield S, Mahboubi S, Shepherd JA, Hangartner TN, Frederick MM, Winer KK, & Kalkwarf HJ. Height Adjustment in Assessing Dual Energy X-Ray Absorptiometry Measurements of Bone Mass and Density in Children. J Clin Endocrin Metab. 2010; 95(3) March1265-1273.
- Kalkwarf H, Gilsanz V, Lappe JM, Oberfield S, Shepherd JA, Hangartner TN, Huang X, Frederick MM, Winer KK, & Zemel BS. Tracking of Bone Mass and Density during Childhood Adolescence. J Clin Endocrinol Metab. 2010 (Apr) 95(4): 1690–1698.
- Short DF, Zemel BS, Gilsanz V, Kalkwarf HJ, Lappe JM, Mahboubi S, Oberfield SE, Shepherd JA, Winer KK, & Hangartner TN. Fitting of bone mineral density with consideration of anthropometric parameters. Osteoporos Int. 2011 22:1047–1057. http://www.ncbi.nlm.nih.gov/pubmed/20495903
- Gilsanz V, Chalfant J, Kalkwarf H, Zemel B, Lappe J, Oberfield S, Handgartner T, & Winer KK. Age at onset of puberty predicts bone mass in young adulthood. J Pediatr. 2011;158(1):100-5.
- Zemel BS, Kalkwarf HJ, Gilsanz V, Lappe JM, Oberfield S, Shepherd JA, Frederick MM, Huang X, LuM, Mahboubi S, Hangartner T, &Winer KK. 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. J Clin Endocrinol Metab, 2011 96:3160-69.
- Shepherd JA, Wang L, Fan B, Gilsanz V, Kalkwarf HJ, Lappe J, Lu Y, Hangartner T, Zemel BS, Fredrick M, Oberfield S, & Winer KK. Optimal monitoring time interval between DXA measures in children. J Bone Miner Res. 2011 Nov;26(11):2745.
- Wren TA, Shepherd JA, Kalkwarf HJ, Zemel BS, Lappe JM, Oberfield S, Dorey FJ, Winer KK, & Gilsanz V. Racial disparity in fracture risk between white and non-white children. J Pediatr. 2012 Sep 3476(12)879.
- Wren TA, Kalkwarf HJ, Zemel BS, Lappe JM, Oberfield S, Shepherd JA, Winer KK, & Gilsanz V. Longitudinal tracking of DXA bone measures over 6 years childhood adolescents. J Pediatr. 2014, 164:1280-85. Accompanying Editorial: Gordon C. Low bone density during childhood: What does it predict? J Pediatr. 2014, 164:1252-1254.
- Kelly A, Winer KK, Kalkwarf HJ, Oberfield S, Lappe JM, Gilsanz V, & Zemel BS. Age-based reference ranges for annual height velocity in U.S. children. J Clin Endo Meteab. 2014, 99: 2104-12.
- Lappe JM, Watson P, Gilsanz V, Hangartner T, Kalkwarf HJ, Oberfield S, Shepherd JA, Winer KK, & Zemel BS. The longitudinal effects of physical activity and dietary calcium on bone mass accrual across stages of pubertal development. J Bone Miner Res. 2015; 30(1); 156-64.
- Short DF, Gilsanz V, Kalkwarf HJ, Lappe JM, Oberfield S, Shepherd JA, Winer KK, Zemel BS, & Hangartner T. Anthropometric models of bone mineral content and areal bone mineral density based on the Bone Mineral Density in Childhood Study. Osteoporosis Int. 2015 26(3);1099-108.
- Ollberding, NJ, Gilsanz,V. Lappe, JM, Oberfield, SE,. Shepherd, JA,.Winer, KK, Zemel, BS, & Kalkwarf, HJ. Reproducibility and intermethod reliability of a calcium food frequency questionnaire for use in hispanic, non-hispanic black, and non-hispanic white youth. J Acad Nutr Diet. 2015; 115(4):519-27.