Role of Cardiometabolic Risk Factors in Childhood Bone Development

• Conditions: Obesity; Cardiovascular Disease; Type 2 Diabetes; Osteoporosis
• Interventions: Other: Observational Study

• Registration Number: NCT02355717
• Lead Sponsor: Augusta University

Brief Summary

The proposed research brings together complementary expertise to systematically elucidate the longitudinal effects of (1) total and regional body fat and (2) the metabolic impairment that accompanies obesity on bone development during growth. The contribution of this research will be significant because it will provide a solid foundation for understanding the influence of fat (total and regional distribution) on overall bone strength, and whether insulin resistance, beta-cell dysfunction, abnormal lipids, and inflammation could be underpinning factors in the fat-bone strength relationship via effects on bone modeling activity. This knowledge will provide critical information needed to maximize potential therapeutic interventions to counter the linked risks of obesity and osteoporosis, both major public health concerns.

Detailed Description

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.

Study Timeline

• Study Start: 2014-12
• Study First Submitted: 2015-01-22
• Study First Submitted QC: 2015-01-30
• Study First Posted: 2015-02-04
• Status Verified: 2019-11
• Last Update Submitted: 2019-11-18
• Last Update Posted: 2019-11-20
• Primary Completion: 2021-12-01
• Study Completion: 2021-12-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 400

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Prospective Cohort	Observational Study	400 otherwise healthy children and adolescents aged 9-15 years will be recruited to participate in a 2-year longitudinal study.

Primary Outcome Measures

Name	Time	Method
Bone mineral mass	Change from baseline bone mineral mass at 2 years	Measurement of bone quantity assessed by peripheral quantitative computed tomography
Bone strength-strain index	Change from baseline bone strength-strain index at 2 years	Measurement of bone quality assessed by peripheral quantitative computed tomography

Secondary Outcome Measures

Name	Time	Method
Serum N-terminal propeptide of type 1 procollagen (P1NP)	Change from baseline P1NP at 2 years	Marker of bone formation as measured in serum
Serum C-terminal telopeptide of type 1 collagen (CTX)	Change from baseline CTX at 2 years	Marker of bone resorption as measured in serum

Trial Locations

Locations (1)

Medical College of Georgia; Augusta University; 🇺🇸 Augusta, Georgia, United States