The function of skeletal adaptation to mechanical load is to adjust the amount and distribution of bone tissue (geometry); such that stresses experienced within the bone are kept within certain physiological limits and fractures are prevented. Genetic, environmental or hormonal factors may cause heterogeneity in this adaptive response, altering geometry and consequently fragility. The purpose of this thesis was to explore the skeletal response to load in vivo, by evaluating stress at the hip under three different conditions: FRACTURE (Study 1), DIABETES (Study 2) and ESTROGEN deficiency (STUDY 3). We studied women 25 years of age or older who participated in the Canadian Multicentre Osteoporosis Study and had available Hip Structure Analysis (HSA) data from baseline dual energy x-ray absorptiometry (DXA) scans. Women were categorized according to fracture status (fracture or no fracture), diabetes status (diabetes or no diabetes) and estrogen use (current users or never users). We computed stress (megapascals=MPa) at the infero-medial margin of the femoral neck in a one-legged
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stance using a 2-D engineering beam analysis. We used linear regression to determine associations between femoral neck stress and each categorical variable. Study 1 (n=2168) demonstrated higher stresses in postmenopausal women with fractures compared to women without fractures (10.57 ± 2.19 vs. 10.30 ± 2.03 MPa; p=0.0031). Study 2 (n=3665) demonstrated higher stresses in women with Type 2 Diabetes Mellitus compared to non-diabetic women (10.98 ± 2.33 vs. 10.57 ± 2.20 MPa; p=0.0194). Study 3 (n=2447) demonstrated higher stresses in postmenopausal women not on estrogen than in premenopausal women (10.66 ± 2.14 vs. 10.09 ± 2.01 MPa; p<0.0001), but no differences in stresses between postmenopausal women on estrogen and premenopausal women (10.16 ± 2.00 vs. 10.09 ± 2.01 MPa; p=0.6102). Since stress is an indicator of underlying geometry, and geometry should be adapted to prevalent loads, higher stress indicates weaker geometry and suggests an impaired modeling response in these three conditions. Compromised modeling has important clinical implications in terms of treatment selection, as individuals with reduced load sensitivity may respond best to metabolic agents that would improve modeling responses to load stimuli.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/35836 |
| Date | 07 August 2013 |
| Creators | Hamilton, Celeste |
| Contributors | Jamal, Sophie, Thomas, Scott |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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