BMDCS was a multicenter, longitudinal study of bone accrual in healthy children and adolescents performed at five U.S. clinical centers (CCs). 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, offered an unprecedented opportunity to identify predictors of peak bone mass, a major determinant of osteoporosis in later adulthood.
The BMDCS provided reference curves for bone accrual, bone accretion velocity, and linear growth velocity that are analogous to the Centers for Disease Control and Prevention’s 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 adverse effects of chronic illness on bone.
Additionally, the results revealed the effects of the timing of pubertal onset on bone density, the need for height adjustment of bone density data in children, and the racial disparities in fracture rates in children. (PMID: 21917867)
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 CCs 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 years old. 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 including children and young adults ages 5-22 years old. Enrollment into this extension phase began in July 2006 and was completed in November 2007, resulting in the addition of 460 children.
Five CCs participated in the study: Children's Hospital of Los Angeles (Los Angeles, CA), Cincinnati Children's Hospital Medical Center (Cincinnati, OH), Creighton University (Omaha, NE), Children's Hospital of Philadelphia (Philadelphia, PA), and Columbia University (New York, NY). The study also included a dual-energy X-ray absorptiometry (DXA) core laboratory and a data coordinating center at the University of California, San Francisco (San Francisco, CA), a DXA quality assurance office at Wright State University (Dayton, OH), and a radiographic core laboratory at Children’s Hospital of Philadelphia. 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.
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 of the lumbar spine and peripheral quantitative CT 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 healthcare providers can use to calculate BMD Z scores for their patients based upon the BMDCS reference data.
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