Department of Medicine

Division of Pulmonary, Allergy, and Critical Care Medicine
3459 Fifth Avenue,
628 NW
Pittsburgh, PA 15213
Phone: (412) 692-2210

The Relationship between Osteoporosis and Phenotypic Heterogeneity in COPD

TRAINEE

Jessica Bon, M.D.

MENTORS

Frank Sciurba, M.D.		G. David Roodman, M.D., PhD

STUDY DESCRIPTION

Chronic obstructive pulmonary disease is the fourth leading cause of morbidity and mortality in the United States with systemic manifestations, such as osteoporosis, skeletal muscle dysfunction, and coronary artery disease contributing significantly to disease burden. The increased prevalence of osteoporosis in COPD presents a particular challenge, as the co-morbidity usually remains asymptomatic until a debilitating fracture occurs. Yet, our understanding of the true prevalence, clinical implications and mechanistic relationship of osteoporosis in COPD patients remains limited. Osteoporosis risk factors, such as steroid use and low body mass index, are frequently present in individuals with severe obstruction. Still, studies have shown an increased prevalence of osteoporosis independent of steroid use and in those with milder airflow limitation, suggesting that pathogenic processes linking COPD to osteoporosis may be independent of severity of airflow obstruction in a subgroup of patients. Furthermore, the cross-sectional nature of most studies provides a snap shot in time, offering little information regarding the natural history of bone loss in COPD. Most epidemiologic studies are either small or focused on poorly characterized individuals with more severe airflow limitation. A longitudinal study of individuals with a wide range of obstruction severity that provides a more precise clinical, physiologic, radiographic and inflammatory phenotypic characterization is critical for the identification of those patients at risk for abnormal bone mineral density and accelerated loss of bone mineral density over time and thus in need of more intensive screening and monitoring of disease.

We hypothesize that the variation in bone mineral density and accelerated loss of bone mineral density over time in COPD patients not on chronic oral steroid therapy is caused by increased bone resorption and is determined by phenotypes identified by unique clinical, radiographic and peripheral inflammatory markers.

Our specific aims are:

• To determine the prevalence of decreased bone mineral density and accelerated loss of bone mineral density over time and its relationship to markers of bone resorption and formation within traditional, spirometrically defined categories of obstruction severity.
• To identify COPD patients at greatest risk for osteoporosis and accelerated loss of bone mineral density over time by classifying patients based on radiographic, clinical, and serum marker phenotypes.
• To compare osteoclast formation and activity and their relationship to serum inflammatory mediators in COPD patients with and without decreased bone mineral density and accelerated loss of bone mineral density.

This project is the basis of a recently submitted NIH K23 Career Development Award application.