COPD and Bone Loss

Osteoporosis describes a progressive loss of bone organic matrix and mineral that reduces the mechanical strength of the tissue to withstand loads, and leads to fractures with low velocity injuries and physiologic loading. Low bone mineral density (BMD) measured by Dual-energy X-ray Absorptiometry (DXA) or other methods is a surrogate marker of osteoporosis and other metabolic bone disease that is a predictor of insufficiency fractures in most populations. Insufficiency fractures are fractures that occur with mechanical loads that are lower than those that would fracture normal bone. They can occur in any bone but are particularly associated with hip, wrist and vertebral fractures in the elderly. The broad category of insufficiency fractures can include the spectrum from local tumors of bone to those from generalized metabolic bone disease, but for our purposes we will focus on generalized bone loss.

Progressive declines in bone mineral density with aging are seen in both men and women of all races. In the general population, otherwise healthy postmenopausal women are identified as a high-risk group for bone loss and associated fractures. Women have lower mean peak bone density than men and have a rapid phase of bone loss in the perimenopause. Osteoporosis in the general population is an age related process that affects women over men (4:1) with other identified risk factors being Caucasian and northern European origins, family history, small stature, early menopause, sedentary lifestyle and low body mass. The disease process is multifactorial with metabolic and hormonal factors (hypogonadism, thyroid disease) also affecting bone turnover along with specific drugs and a history of smoking. There are also racial differences in bone density loss, with African Americans having lower risk of reduced bone density due to higher peak bone density and Asians appearing to have intermediate risk ([1]).

Insufficiency fractures are associated with increased death and disability, and bone loss appears to be an important marker of biologic decline in aging. Hip fractures are associated with a 24% mortality within 12 months after fracture and more than half the affected individuals do not return to their pre-injury walking status ([2], [3]). Medicare patients with vertebral compression fractures have a 23% increased risk of death compared to controls ([4]).

In this issue of COPD: Journal of Chronic Obstructive Pulmonary Disease Li et al add important information to the link between the musculoskeletal system and COPD, with their report that men and African Americans affected by severe COPD are at risk of both significant bone loss and insufficiency fractures, in striking contrast to non-COPD populations. Previous authors have observed an association between osteoporosis and COPD, emphasizing the role that nutrition, steroids, and inactivity may play in bone loss with COPD ([5], [6], [7], [8]). This current study highlights the relationship by demonstrating increased bone loss in two groups that are less affected by age-related bone loss, and again raises important questions about why a lung disease would affect bone turnover. Their report (and others) that steroid use is not a sole predictor of bone disease within lower risk males and African-Americans with COPD weakens the case for bone loss being simply a drug side effect. Severe lung disease both in COPD and cystic fibrosis is strongly correlated with bone loss ([6]) and interestingly inflammatory bowel disease likewise has a strong association with bone loss ([9]).

Several potential questions stand out for further study. Are there common mechanisms that we can consider, such as tissue destruction and failure of homeostasis within the extracellular matrix, in a systemic inflammatory milieu, which would link the disease processes? How do the known inflammatory pathways of COPD affect bone? Can osteoporosis in COPD shed light on the general problem of bone matrix turnover and mineralization? How are bone loss and muscle loss related in COPD?

For clinicians this study highlights the importance of diagnosis and prevention of bone loss in COPD patients. Screening should be early and relatively often. Currently screening recommendations for asymptomatic healthy individuals are based on assumptions of disease prevalence and severity that are very different from those in COPD. Follow-up intervals should be modified from that of healthy patient screening to time frames that reflect the severity of lung disease, how much bone loss has occurred and whether steroids are being used. At a mean age of just under 60 years in this study only 3% of the subjects did not have either osteoporosis or osteopenia. Screening for COPD patients should start when the diagnosis of smoking related lung disease is made and treatment should be initiated promptly to minimize fractures.

Prevention strategies could reasonably include calcium and vitamin D supplementation, pulmonary rehabilitation focused on increasing weightbearing exercise, judicious use of steroids, improved nutrition and control of chronic infections and inflammation. Prospective studies are needed to evaluate the effectiveness of these strategies in the context of COPD. Anti-resorptive and anabolic treatments to reduce/restore bone loss likewise are appropriate to reduce the morbidity of fractures and prospective studies are needed to determine the most effective regimens in this disease state.

As high resolution CT scanning of the chest is increasingly used to diagnose and quantify the extent of lung disease in COPD, there are opportunities to evaluate the vertebral column for both bone density and previous fractures whenever chest CT is obtained to assess the extent of pulmonary disease. Reconstructed images can be used to identify vertebral fractures and progressive thoracic kyphosis that may affect lung function. Quantitative CT scanning can provide highly precise measures of bone density that may reveal important longitudinal data about bone loss and the activity of lung disease.

Associating this data with information about inflammatory markers, bone turnover markers and disease severity would provide valuable insights into the relationship of bone and lung disease. Validation of muscle quantitation on chest CT scans would add greater depth of understanding of cachexia in the context of both lung disease and bone loss. All of these investigations would broaden and deepen our understanding of the spectrum of COPD as a multisystem disease. Finally, more studies are needed to understand the prevalence of bone loss in smokers without lung disease—to inform clinicians of appropriate screening patterns for these higher risk individuals and to provide a comparison group for the unique events involved in COPD progression.