Bone Development Clinical Trial
Official title:
Obesity and Bone Development in Young Girls
Obesity during adolescence, a critical time for bone development, may impair mineral accrual and reduce bone strength, leading to greater fracture risk during adolescence and later in life. This study seeks to determine the effect of obesity and accompanying metabolic changes (insulin resistance and inflammation) on bone mineral accrual and related changes in structure and strength in young girls. The information is critical to developing effective prevention strategies to counter the linked risks of obesity and osteoporosis, both major public health concerns.
The pediatric obesity epidemic continues unabated. Its cardio-metabolic complications are
undisputed, including inflammation, insulin resistance (IR), glucose intolerance and greater
prevalence of type 2 diabetes (T2D) in youth. We contend an equally serious consequence of
these obesity co-morbidities is their detrimental effects on bone development during
adolescence, a critical time for mineral accrual and architectural modeling that underlies
bone strength and fracture risk. This proposition has received little attention and the
sparse results are mixed, with reports of augmented and impaired mineralization. In
contrast, animal data demonstrates reduced mineral accrual and compromised architecture with
insulin resistance and chronic inflammation. The conflicting results in youth are likely due
to mixed samples and analyses that commingle obese youth with metabolic complications with
so called metabolically healthy obese youth and the use of technology (i.e., dual energy
x-ray absorptiometry, DXA) to measure bone outcomes that is confounded by the very changes
that investigators seek to detect. We posit that the positive mechanical effect of excess
adiposity on bone is countered by chronic low-grade inflammation and IR so that obese youth
with these metabolic complications suffer impaired bone development whereas obesity in
otherwise metabolically healthy youth augments development. A thorough understanding of the
effects of adiposity and its co-morbidities on bone development is crucial to the
development of efficacious interventions aimed at maximal mineral accrual and bone modeling.
Thus, we propose primary aims designed to clarify the effects of obesity, insulin resistance
and inflammation on bone around the time of peak height velocity. Adipose tissue (AT)
distribution undoubtedly matters, especially abdominal visceral AT and skeletal muscle fat
content, both strongly related to insulin resistance. Failure to characterize fat
distribution is another important limitation of past studies. Consequently we will assess
the effect of visceral AT and skeletal muscle fat along with whole body fatness and propose
secondary aims designed to develop safe, cost effective methods that we and others can use
for estimating AT distribution, a critical component of risk that has rarely been studied in
youth relative to bone development.
Primary Aims:
1. Assess the associations of total and regional adiposity (visceral AT and leg muscle fat
content), insulin resistance, and inflammation with bone mass, density, structure and
strength in normal weight, overweight, and obese pre-menarcheal girls
2. Assess the effects of total and regional adiposity, insulin resistance, and
inflammation on bone development (i.e., 2 year changes in bone parameters) in normal
weight and obese pre-menarcheal girls.
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Observational Model: Cohort, Time Perspective: Prospective
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