© 2004 American Thoracic Society doi: 10.1164/rccm.2410001
Musculoskeletal Effects of Chronic Obstructive Pulmonary DiseasePrevalent, Linked, but IgnoredUniversity of Buffalo SUNY Buffalo, New York The musculoskeletal system is among the extrapulmonary organ systems most frequently affected by chronic obstructive pulmonary disease (COPD) (1, 2). Initially described as weight loss and cachexia, the involvement of the musculoskeletal apparatus in COPD is now better understood as a loss of fat-free mass (FFM) and bone mineral density (BMD) (3, 4). Previous studies have described these processes separately and established the body mass index (BMI) as a predictor of loss of FFM and BMD (4, 5). In this issue of the Journal (pp. 1286–1293) Bolton and coworkers have taken this a step further, demonstrating that these processes are not only interrelated, but are often inapparent, that is, existing in patients with COPD with a normal BMI (6). In the study by Bolton and colleagues, 41% of patients with COPD had decreased FFM (defined as below the 5th percentile of comparable healthy control subjects), whereas 32% had osteoporosis (defined by T scores of < 2.5) (6). What is important is the high frequency of these findings in relatively unselected primary care patients representing the spectrum of severity of COPD. Furthermore, a low FFM was seen in 21% and osteoporosis was seen in 25% of patients with a normal BMI, emphasizing the inapparent nature of these processes. Clearly, if we were to start screening and treating patients with COPD for these complications, this study demonstrates that measurement of BMI is not an adequate screening tool. Loss of FFM and BMD were interrelated in this study (6). Although one could speculate that common mechanisms may be involved, alternative explanations exist. There are several potential causes of BMD and FFM loss in patients with COPD, including inactivity, systemic inflammation, corticosteroid use, nutritional impairment, hypogonadism, and smoking (4, 7–9). Even though the authors did study systemic inflammation, in the absence of a systematic assessment of the other potential causes, it is difficult to conclude that a common mechanism is causing BMD and FFM loss in COPD. Why should increasing severity of COPD be associated with decreasing FFM and BMD? Again, several of the above mechanisms can come in to play with increasing severity of COPD. These would include progressive deconditioning and inactivity, greater number of exacerbations, increased use of corticosteroids, and increasing systemic inflammation. Additional studies to determine the important mechanisms will be important to allow specific therapy to be chosen. For example, if inactivity is the major mechanism, then pulmonary rehabilitation should have beneficial effects on BMD and FFM. On the other hand, if systemic inflammation is responsible, then antiinflammatory therapy may be indicated.
Systemic inflammation and oxidative stress has been consistently identified in stable COPD (1, 10). Of the proinflammatory markers elevated in COPD, tumor necrosis factor- What are the clinical implications of the burgeoning evidence that loss of FFM and osteoporosis are prevalent in COPD? Should we start screening patients with COPD for these disorders and treat accordingly? Though the ERS/ATS guidelines recommend screening for loss of FFM among patients with COPD, the results of nutritional supplementation have been disappointing, and clear benefits have not been demonstrated (11, 12). On the other hand, though effective therapy is available for osteoporosis, none of the current guidelines for COPD or osteoporosis recommend screening for osteoporosis among patients with COPD (unless they are on chronic systemic corticosteroids) (11, 13–15). The lack of emphasis on screening for osteoporosis in COPD may relate to inadequate knowledge of the clinical consequences of the decrease in BMD in these patients, a limitation well illustrated by the study of Bolton and coworkers, where no information is provided regarding the incidence of bone fractures in the population studied (6). Furthermore, the costs of screening and treating osteoporosis in patients with COPD are likely to enormous, given the prevalence of this disease. Future research should focus on demonstrating the clinical implications of low BMD and benefit with treatment in prevention of bone fractures in COPD. Given the prevalence of osteopenia and osteoporosis in COPD, should we be concerned about the small detrimental effects on BMD of inhaled corticosteroids in these patients? An increased prevalence of bone fractures has not been demonstrated in prospective trials of inhaled corticosteroids (16). Another consideration is the recent demonstration of a systemic antiinflammatory effect of inhaled steroids, which may be beneficial if systemic inflammation is indeed responsible for the musculoskeletal effects of COPD (17). Furthermore, a decrease of the frequency and intensity of exacerbations of COPD with inhaled corticosteroids, with a concomitant decrease in periods of inactivity and use of systemic steroids, may readily counteract the detrimental effect of these drugs on BMD. With numerous studies documenting decreased BMD and FFM in COPD, future research should focus on understanding of the mechanisms involved, with the promise of specific mechanism directed therapy. In the interim, pulmonary rehabilitation and minimization of systemic corticosteroids should help counteract this important systemic manifestation of COPD. FOOTNOTES Conflict of Interest Statement: S.S. has received research funding from GlaxoSmithKline (GSK) and has received honoraria from GSK and AstraZeneca for speaking or attending conferences. REFERENCES
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