Jarvis Smith (Dissertation Proposal Defense) rescheduled for Feb 9th at 11 AM in
Townsend Hall 049
Title: Bone Size, Bone Distribution, Intermuscular Adipose Tissue and Adipose TissueDerived Hormones in Children with Quadriplegic Cerebral Palsy
Date: Thursday, 1/27/11
Time: 1:00 pm
Place: 225 McDowell Hall
Committee: Christopher Modlesky, PhD (chair), David Edwards, PhD, Kurt Manal, PhD,
Freeman Miller, MD
Abstract: Children with quadriplegic CP, those who are unable to ambulate
independently, have high fracture rates in the distal femur. Although their bone fragility
is related to low areal bone mineral density (aBMD) estimated using dual-energy X-ray
absorptiometry (DXA), there is a substantial overlap in those who do and do not fracture.
The overarching aim of this proposal is to determine if bone size, bone
distribution and adiposity contribute to bone fragility in children with quadriplegic CP.
Some investigators have reported reduced bone size in the lower extremities of children
with CP. However, DXA-based estimates of bone area in the distal femur are
inconclusive which may be due to the inability of DXA to assess bone in three
dimensions. Conversely, magnetic resonance imaging (MRI) provides more valid
estimates of bone size than DXA because it assesses bone in three dimensions. Another
potential factor contributing to the bone fragility of children with CP is trabecular bone
microarchitecture (TBM). Underdeveloped TBM has been observed in the distal femur of
children with quadriplegic CP.
However, because it is suspected that most fractures occur at the junction between the
metaphysis and diaphysis, it is plausible that the underdevelopment is greater in the
region closer to the diaphysis than the growth plate. Additional factors that potentially
contribute to bone fragility in children with quadriplegic CP include abnormal adipose
tissue (AT) quantity and distribution. Increased adiposity is associated with
low aBMD and increased fracture risk in children with CP. Furthermore, recent reports
indicate significant AT infiltration of skeletal muscle at the midthigh of children with
quadriplegic CP. The mechanism(s) mediating the influence of AT on bone are unknown;
however, leptin and adiponectin, bioactive AT-derived hormones, are suspected to be
important contributors. The aims of this proposal are: 1) to identify differences in bone
area between children with quadriplegic CP and typically developing children using
MRI; 2) to examine the pattern of TBM underdevelopment in the distal femur of children
with quadriplegic CP; 3) to examine the relationship between midthigh intermuscular AT
(IMAT) and TBM in the distal femur of children with quadriplegic CP; and 4) to examine
the relationships between AT-derived hormones, and TBM in children with quadriplegic
CP.
To address the specific aims, magnetic resonance images collected from children with
quadriplegic CP and typically developing children of similar age will be used to assess
TBM in the distal femur and IMAT in the midthigh. Fasting blood samples collected
from the same subjects will be used to assess serum leptin and adiponectin. The proposed
work is significant because it will help us identify potential contributors to bone fragility
in children with CP.