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Factors associated with longitudinal bone mineral density loss in a tobacco-exposed cohort

Field, Jessica (2015) Factors associated with longitudinal bone mineral density loss in a tobacco-exposed cohort. Master's Thesis, University of Pittsburgh. (Unpublished)

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The prevalence of low bone mineral density (BMD) is increased in individuals with chronic obstructive pulmonary disease (COPD) independent of traditional osteoporosis risk factors. COPD-specific guidelines for BMD assessment do not exist and general guidelines for osteoporosis screening do not recognize COPD as a risk factor for fracture. Nonetheless, osteoporotic fractures are of major public health importance given the negative impact of fractures on morbidity and mortality in COPD patients. Furthermore, increased bone turnover independently contributes to fracture risk yet cannot be determined by cross-sectional dual x-ray absorptiometry (DXA) assessment alone. We established a longitudinal cohort of male and female smokers with and without smoking-related lung disease (i.e. emphysema or airflow obstruction) to determine factors related to accelerated BMD loss in smokers. We obtained baseline and 2-year measurements of pulmonary function, BMD, radiographic emphysema, and demographic and clinical characteristics. We assayed baseline blood samples for markers of bone metabolism, matrix metalloproteinases (MMP) and their inhibitors, interleukin-6, and tumor necrosis factor alpha. Of those with lung disease, 48.6% had evidence of osteopenia or osteoporosis at baseline compared to 29.4% without lung disease (p=0.01). The incidence of accelerated hip or lumbar spine BMD loss was 33.8% in subjects with lung disease versus 19.6% in those participants without lung disease (p=0.01). Both type I collagen C telopeptide (CTx), a marker of bone resorption, and radiographic emphysema were independent predictors of accelerated BMD loss (OR 5.5 [2.1,14.4] for moderate/severe emphysema; OR 2.9 [1.3,6.4] for highest tertile CTx) when adjusted for age, gender, steroid use, and current smoking status. Tissue inhibitor of matrix metalloproteinase (TIMP) 4 was independently associated with BMD decline at the hip (p=0.04) and higher in subjects with emphysema progression (p=0.03). TIMP1 and MMP7 levels were also higher in subjects with emphysema progression. These findings suggest that accessible and easily measured biomarkers may be used to guide early and serial DXA BMD assessments in a subset of smokers at risk for accelerated BMD decline. TIMP4 and MMPs may further be involved in the regulation of lung and bone matrix degradation in individuals with emphysema-related BMD decline.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Field, Jessicajmm113@pitt.eduJMM113
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairDiergaarde, Brendabbd3@pitt.eduBBD3
Date: 28 September 2015
Date Type: Publication
Defense Date: 31 July 2015
Approval Date: 28 September 2015
Submission Date: 20 July 2015
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 33
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Epidemiology
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: Chronic Obstructive Pulmonary Disease Osteoporosis Emphysema Systemic inflammation
Date Deposited: 28 Sep 2015 18:00
Last Modified: 15 Nov 2016 14:29


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