Role of Cardiometabolic Risk Factors in Childhood Bone Development

The overall goal of this study is to clarify the relationship of adiposity with bone
development during adolescence, and to explicate the mechanisms that regulate the effect of
excess adiposity on bone. In this effort, we will conduct a 2-year longitudinal study in 400
children and adolescents aged 9-15 years. Using the peak adolescent growth period as a model
for probing determinants of bone health may allow for a clearer picture of the processes
that regulate bone development, as these processes are highly active at this growth stage.
Unlike other studies with surrogates for adiposity, we plan to measure total and central
adiposity directly, using dual energy X-ray absorptiometry (DXA) and magnetic resonance
imaging. Both bone quantity and bone quality, the two principal determinants of bone
strength, will be assessed by peripheral quantitative computed tomography (pQCT) at
weight-bearing (tibia) and non-weight-bearing (radius) skeletal sites. Peripheral QCT
provides 3-dimensional bone measurements that are not confounded by changes in bone size, a
significant confounder of most past studies, which have relied on 2-dimensional bone imaging
techniques. To identify mechanistic factors, which may explain the effect of adiposity on
bone development, we will measure arterial stiffness, endothelial function, and fasting
levels of glucose, insulin, lipids, and C-reactive protein (CRP) to assess how vascular
dysfunction, insulin resistance, abnormal lipids, and inflammation are related to bone
modeling activity, as measured by serum markers of bone formation and resorption. All
measurements will be assessed at baseline and after 1 and 2 years of follow-up.

Inclusion Criteria:

1. Otherwise healthy children and adolescents between 9 and 15 years old

2. Subject and parent/guardian understands the study protocol and agrees to comply with
it

3. Informed Consent Form signed by the parent/guardian and assent signed by the subject

Exclusion Criteria:

1. Subjects with (a history of) metabolic or gastrointestinal diseases including hepatic
disorders

2. Subjects presenting chronic degenerative and/or inflammatory diseases

3. Subjects receiving systemic treatment or topical treatment likely to interfere with
evaluation of the study parameters (salicylates, antibiotics)

4. Subjects receiving corticosteroid treatment

5. Subjects using oral anticoagulants

6. Subjects who have participated in a clinical study more recently than one month
before the current study