| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Guest Access | Sign In via User Name/Password
|
|
|
|||||||
Guest Access | Sign In via User Name/Password |
|||||||||
Chapel Hill, NC
Dr. Aris is Associate Professor of Medicine and Medical Director of the Lung Transplant Program, University of North Carolina at Chapel Hill. Dr. Donohue is Professor of Medicine and Division Chief of Pulmonary Medicine, University of North Carolina at Chapel Hill. Dr. Ontjes is Professor of Medicine, University of North Carolina at Chapel Hill.
Correspondence to: Robert M. Aris, MD, CB# 7020, 420 Womack Building, Chapel Hill, NC 27599-7020
In this volume of CHEST (see page 89), Johannes et al have examined the risk of nonvertebral fracture related to inhaled corticosteroid (ICS) exposure among adults with chronic lung disease followed up in a managed-care setting. They found no increased fracture risk with any of this class of drugs and no dose-response curve. They concluded that "concern about nonvertebral fracture risk should not strongly influence the decision to use recommended doses of ICS in adults with chronic lung disease." Studies of this type are very important to determine the role of ICSs in fractures. The authors should be credited for their diligent work.
The issue of ICSs and fractures is complex and controversial mainly because lung specialists view them in such high regard. More than 100 publications have cited the value of ICS in the management of chronic lung disease, mainly asthma. They are used widely in COPD, sarcoidosis, and a variety of other disorders as well, but with less proof of overall efficacy than in asthma.1 They have been fully embraced as asthma disease modifiers and lifesavers by the pulmonary community for almost 2 decades. Plain and simple, they work. For COPD, they have some benefits, but are less effective. ICS monotherapy in COPD is effective at increasing FEV1 by small amounts, reducing COPD exacerbations, and improving health status, but not reducing FEV1 decline over time.2
In 2003, the "Systematic Review of the Evidence Regarding Potential Complications of Inhaled Corticosteroid Use in Asthma" was published in CHEST in collaboration with the American College of Chest Physicians, the American Academy of Allergy, Asthma, and Immunology, and the American College of Allergy, Asthma, and Immunology.3 It concluded that "the preponderance of evidence supports a conclusion that the proven clinical effectiveness of ICS treatment decidedly outweighs the proven risks." This conclusion illustrates the "bias" (or, should we say, inclination) that we have as lung specialists. Even when we are put to task, as the title suggests, to review the potential complications of ICSs, we conclude that their benefits outweigh their risks without offering a risk-modification strategy. It is possible for us to accept their benefits along with their risks and simultaneously mollify those risks (having our cake and eating it too).
While it is beyond the scope and word limits of this editorial to examine the adverse impact on bone health of ICSs in a scientifically rigorous fashion, such an examination is critical. And fortunately, a meta-analysis of all rigorous, controlled studies of ICSs and bone density or fractures (including randomized controlled trials, and prospective, retrospective and cross-sectional analyses) has been performed by Richy et al,4 who concluded from this meta-analysis that ICSs were associated with a 1.2- to 1.8-times increased risk of vertebral fracture and a 1.6-times increased risk of hip fracture. Furthermore, ICS use was associated with a lower bone density at the spine and hip as well as lower serum levels of the bone formation markers, osteocalcin and procollagen type 1 C-terminal propeptide. Budesonide at a mean (SD) daily dose of 686 ± 158 µg, beclomethasone at 703 ± 23 µg, and triamcinolone at 1,000 ± 282 µg were found to adversely affect bone density and bone formation markers in patients with asthma and COPD. These doses are at the upper end, but below the maximum, of the therapeutic dosing range, and well within the doses prescribed in patients with advanced or difficult-to-control lung disease. Triamcinolone use was associated the highest overall bone loss, followed by beclomethasone and budesonide, but the most important correlate of bone loss was the dose used, not the brand name of the ICS. There was insufficient data on fluticasone to draw any conclusions, probably because it has been available in the marketplace for a shorter period of time.
In this editorial, we would like to draw attention to several important conclusions about ICSs and bones. First, ICSs have a far less (in the range of fivefold to tenfold) adverse effect on bone than their oral counterparts and are very safe in low-to-moderate doses. Second, bone loss and fractures occur at higher rates in our COPD and asthma patients receiving high-dose, long-term ICSs; and ICSs clearly play a role. However, it is doubtful that these problems are entirely due to ICSs. Additional risk factors including age, severity of chronic lung disease, smoking, and physical inactivity can confound the analyses even when oral corticosteroid use is eliminated or controlled for. Patients with chronic respiratory disease, as in individuals with other chronic maladies, are at an increased fracture risk even if they do not use oral corticosteroids or ICSs.56 Thus, it is necessary to risk stratify our patients to ultimately understand the magnitude of the effect of ICSs on bones for any given patient. A young, premenopausal asthmatic patient may need to take high-dose ICSs for 15 years to see a doubling of fracture risk.7 An older patient with COPD is already at a higher fracture risk due to age and chronic disease, and long-term ICS use may further exacerbate this risk.2 Last, osteoporosis is a disease that is similar in magnitude to COPD in the United States in terms of morbidity, mortality (> 100,000 deaths annually), and health-care costs (approximately $15 billion annually),8 and therefore deserves our attention in terms of disease prevention and treatment.
Translating this knowledge into clinical practice finally gets at the question posed in the title of this editorial. While many articles are written in this area, few offer an answer to the question, "What to do?" Published guidelines indicate that patients receiving long-term ICSs should be screened for bone loss.9 Fortunately, a simple, inexpensive, and fast test (dual-energy radiograph absorptiometry [DXA]) can take much of the guesswork out of fracture risk assessment. If we simply screen patients at risk for accelerated bone loss (long-term [oral or inhaled] corticosteroid users, postmenopausal [or hypogonadal] status, presence of advanced lung disease, or a history of fractures) with a spine and hip DXA, we can quantify risk with a reasonably high degree of assurance since bone density is the most robust predictor of fracture in our society. Then, we need to act to prevent fractures by either referring our patient to a specialist or implementing prevention and/or treatment with a follow-up algorithm to maintain or improve bone density (as a surrogate to reduce fractures). While our old standby of calcium (daily intake > 1,000 mg) plus vitamin D (daily intake > 800 IU) is sufficient for the prevention of bone loss in healthy persons, they will not prevent or treat bone loss or osteoporosis in patients receiving long-term, high-dose ICSs. Most studies to date indicate that patients with established osteoporosis (spine or femur T score < – 2.0 [National Osteoporosis Foundation guidelines] or < – 2.5 [World Health Organization guidelines]) or a history of fracture with osteopenia (T score < – 1.0) would benefit from a bisphosphonate. Patient choice and third-party payer reimbursement are important issues when it comes to choosing which bisphosphonate to use. An oral bisphosphonate (alendronate or residronate) administered weekly or an IV bisphosphonate (zolendronic acid or pamidronate) administered quarterly to annually are considered equally effective. Last, weight-bearing exercise is helpful in preventing bone loss and should be included as an adjunct to pharmacologic therapy.
ICSs are the mainstay of therapy for many chronic lung diseases. Long-term, high-dose ICSs (of which many of our patients are taking) are associated with increased fractures. While the results of the article by Johannes et al are "negative," we wholeheartedly agree with the final conclusion of their article quoted above. Unlike many authors who usually want to say that their study provides a definitive answer to the question posed, Johannes et al had the wisdom to draw a conclusion based not only on the data of their group but by considering their data in the context of the many studies in this area by others. As lung specialists, we need to use the lowest and, simultaneously, most effective dose of ICS to control the underlying disease consistent with the asthma and COPD management guidelines promulgated by the National Heart, Lung, and Blood Institute and the World Health Organization. In addition, we need to screen and initiate both preventative and therapeutic efforts to patients with chronic lung disease receiving long-term, high-dose ICSs to lower the rate of fractures. We can have our cake and eat it too.
References
This article has been cited by other articles:
|
|
 |
|
  P. Vestergaard, L. Rejnmark, and L. Mosekilde Fracture Risk in Patients With Chronic Lung Diseases Treated With Bronchodilator Drugs and Inhaled and Oral Corticosteroids Chest, November 1, 2007; 132(5): 1599 - 1607. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
