BMDCS was a multicenter, longitudinal study of bone accrual in healthy children and adolescents performed at five U.S. clinical centers. Detailed information about the study participants, inclusion/exclusion criteria, and study procedures have been published. The study provided longitudinal measurement of bone mass, linear growth, sexual and skeletal maturation, dietary intake, physical activity, and health history. This study, supported through NICHD's Pediatric Growth and Nutrition Branch (PGNB), 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 linear growth and weight gain curves for children and adolescents. The BMDCS reference curves provide the “gold standard” for normal bone accrual and enable practitioners to identify any adverse effects chronic illness has on bone.
Additionally, the results also revealed the effects of pubertal onset timing on bone density and linear growth, the need for height adjustment to analyze dual-energy X-ray absorptiometry scans in children, and the racial disparities in fracture rates in children. 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 primary goal of BMDCS was to obtain 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 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.
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 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.