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• W2023131977 abstract "COPD is an inflammatory condition of the lung, and, over the past decade, it has been increasingly recognized for its systemic inflammation and extrapulmonary manifestations.1Rabe KF Hurd S Anzueto A et al.Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary.Am J Respir Crit Care Med. 2007; 176: 532-555Crossref PubMed Scopus (4432) Google Scholar The levels of common proinflammatory molecules, such as interleukin 1, interleukin 6, tumor necrosis factor α, and C-reactive protein, are elevated in the blood, and some proinflammatory molecules are present in large amounts in the lung tissues or BAL fluid.1Rabe KF Hurd S Anzueto A et al.Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary.Am J Respir Crit Care Med. 2007; 176: 532-555Crossref PubMed Scopus (4432) Google Scholar Whereas osteoporosis is multifactorial in its etiology, it is most commonly seen in individuals who are elderly, have chronic illnesses, or have chronic systemic inflammation.2Robbins J Aragaki AK Kooperberg C et al.Factors associated with 5-year risk of hip fracture in postmenopausal women.JAMA. 2007; 298: 2389-2398Crossref PubMed Scopus (218) Google Scholar Biochemically, proinflammatory molecules have been shown to favor a loss of bone mineralization.3Mundy GR Osteoporosis and inflammation.Nutr Rev. 2007; 65: S147-S151Crossref PubMed Google Scholar Unfortunately, patients who have moderate-to-severe COPD have many of the clinical features that predispose them to osteoporosis, by virtue of being elderly or chronically disabled, and having chronic systemic inflammation. In this issue of CHEST (see page 1456), Ferguson et al4Ferguson GT Calverley PM Anderson JA et al.Prevalence and progression of osteoporosis in patients with COPD: results from TORCH.Chest. 2009; 136: 1456-1465Abstract Full Text Full Text PDF PubMed Scopus (207) Google Scholar have reported on the prevalence and progression of osteoporosis in a North American cohort of subjects with moderate-to-severe COPD from the Towards a Revolution in COPD Health (TORCH) study. A total of 658 subjects were followed up yearly for 3 years with measurements of bone mineral density (BMD) of the hips and lumbar spine using dual-energy x-ray absorption scanning. The study achieved a completion rate of 43%. Sadly, they have once again confirmed for clinicians that the uptake of important medical facts is slow and inadequate. Although osteoporosis is costly to the health-care system (the cost has been estimated to be approximately $19 billion per annum in the United States by the National Osteoporosis Foundation [http://www.nof.org/osteoporosis/diseasefacts.htm]) and predisposes individuals to serious fractures that contribute in some cases to premature death,2Robbins J Aragaki AK Kooperberg C et al.Factors associated with 5-year risk of hip fracture in postmenopausal women.JAMA. 2007; 298: 2389-2398Crossref PubMed Scopus (218) Google Scholar it is grossly underrecognized. The authors4Ferguson GT Calverley PM Anderson JA et al.Prevalence and progression of osteoporosis in patients with COPD: results from TORCH.Chest. 2009; 136: 1456-1465Abstract Full Text Full Text PDF PubMed Scopus (207) Google Scholar have found that women were more affected, but osteoporosis and osteopenia were common in the study population. For example, 23% of the subjects had osteoporosis, 42% had osteopenia, and 65% had osteoporosis or osteopenia at the time of study enrollment. Surprisingly, only 7% and 23% of the subjects, respectively, were receiving therapy with bisphosphonates or a BMD medication prior to the study, and 11% and 9% of subjects, respectively, started to receive therapy with bisphosphonates or a BMD medication during the trial period of 3 years. When the placebo-controlled arm was compared to the active treatment groups (salmeterol, fluticasone propionate [FP] alone, and FP/salmeterol combination), the authors found no deleterious effects of FP on the rate of BMD loss in the hip and lumbar spine, or there was no increase in the incidence of fractures, over the observation period of 3 years. We may wish to conveniently conclude that inhaled corticosteroid (ICS) use does not cause thinning of the bone. However, it is more appropriate to think about the complexity of the situation. The administration of systemic corticosteroids (SCSs) at a larger than minimum dose, and particularly if they are administered over a long period of time, is generally thought to cause osteopenia and osteoporosis.2Robbins J Aragaki AK Kooperberg C et al.Factors associated with 5-year risk of hip fracture in postmenopausal women.JAMA. 2007; 298: 2389-2398Crossref PubMed Scopus (218) Google Scholar Whether ICS therapy produces adequate blood levels that can adversely affect BMD is not certain, but even a small effect over an extended period of time may produce serious side effects. In terms of benefits, ICSs have been shown to reduce the frequency of acute exacerbations in patients with moderate-to-severe COPD, and this would benefit the individual by reducing the use of SCSs for rescue.5Calverley PM Anderson JA Celli B et al.Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease.N Engl J Med. 2007; 356: 775-789Crossref PubMed Scopus (2838) Google Scholar ICS therapy has been shown to improve the quality of life of the individual,5Calverley PM Anderson JA Celli B et al.Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease.N Engl J Med. 2007; 356: 775-789Crossref PubMed Scopus (2838) Google Scholar and this would add to the mobility and physical activities of the individual. Finally, COPD lungs are a source of proinflammatory molecules and a contributor to systemic inflammation. If ICS therapy can reduce the lung source of these molecules, it may actually be beneficial to the bones.6Sin DD Man SF Marciniuk DD et al.The effects of fluticasone with or without salmeterol on systemic biomarkers of inflammation in chronic obstructive pulmonary disease.Am J Respir Crit Care Med. 2008; 177: 1207-1214Crossref PubMed Scopus (178) Google Scholar This current trial is complicated by a multitude of confounding factors, such as prior and concurrent use of powerful BMD medications, the use of ICSs and SCSs, smoking practice, and differences in the nutrition and physical activity levels of the individuals. The high prevalence of osteoporosis and osteopenia in this population and, more importantly, the small sample size, due to a dropout rate of > 50% in the clinical trial, do not help to provide a simple conclusion. Moreover, more women in the FP-based arms of the trial began to receive a BMD-sparing drug during follow-up than those in the placebo arm (34% vs 19%, respectively; relative risk, 1.79; p = 0.03), which further complicates the BMD data. Predictably, it would be very hard to tease out the medication effect of ICS therapy. On the basis of the evidence presented, while this trial has added to the body of literature, it has not resolved the controversy of whether or not ICS therapy aggravates or causes osteoporosis. It is fair to say that conducting a trial that will yield clinically relevant end points for osteoporosis in COPD patients is no easy task, and that it may not be done any time soon. So, what lessons can we take away from the TORCH study? As a community of medical specialists, we should bear in mind the high prevalence of osteopenia and osteoporosis in COPD patients when we meet our next patient, and we should look for these related diagnoses. In the TORCH study, the authors reported a decline of about '3% of BMD over 3 years in subjects with moderate-to-severe COPD, but medications could increase BMD for a net gain of about 4% over the same period. When osteopenia or osteoporosis is confirmed, we should seriously consider the use of a BMD-sparing medication, regardless of whether or not the subject is receiving therapy with an ICS." @default.
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• W2023131977 title "Thinning Bone and Inhaled Corticosteroid in COPD" @default.
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