TOKYO—Osteoporosis occurs more frequently in people with chronic obstructive pulmonary disease (COPD) than in those with asthma, even though the latter group typically uses inhaled corticosteroids more often and in higher total doses. Studies have suggested that the presence of osteoporosis in patients with COPD has several causative factors—not only corticosteroid use but also low body mass index (BMI), malnutrition, and smoking. Furthermore, COPD itself may be a risk factor.

Hideki Katsura, MD, and Kozui Kida, MD, both from the Pulmonary Division of the Tokyo Metropolitan Geriatric Medical Center, conducted a cross-sectional survey of 44 elderly women, 20 with COPD and 24 with asthma.[1] Patients were asked about their smoking history, current and past use of systemic and inhaled corticosteroids, other drug regimens, and other possible risk factors for osteoporosis, such as family history and menopausal status. To determine what factors other than systemic corticosteroid use influence bone mineral density (BMD), only patients who had never received those drugs were included.

Pulmonary function tests were performed, and blood and urinary concentrations of bone metabolism markers were measured. Bone mineral content and BMD were measured using dual-energy x-ray absorptiometry. Osteoporosis was defined as lumbar BMD less than 70% of the mean BMD for young adults.

OSTEOPOROSIS DESPITE STEROID USE (OR NONUSE)

Compared to asthma patients, those with COPD were significantly leaner and had a lower BMI. All patients in the asthma group and three quarters of those in the COPD group were using inhaled corticosteroids. The duration of use and total accumulated dose were significantly higher in asthma patients. Despite this, total body and lumbar spine BMD was significantly lower in the COPD patients. In fact, 50% of the patients with COPD were diagnosed with osteoporosis, compared with 21% of the asthma patients.

The prevalence rate for having more than one vertebral fracture was 40% in patients with COPD, compared with 15% in patients with asthma. Except for BMI, no other factors were correlated with BMD.

Elderly women have a high incidence of osteoporosis regardless of whether they have COPD. In 1999, however, a study by Iqbal et al[2] showed that the prevalence of osteoporosis was four times greater in men with COPD than in controls, even though none of the COPD patients had received systemic corticosteroids.

“Both men and women with COPD are at increased risk [for osteoporosis] compared to the normal population,” observed Diane M. Biskobing, MD, Associate Professor of Medicine at Virginia Commonwealth University, in Richmond. “But the rates in postmenopausal women with COPD will be higher because [they have] other risk factors as well.”

Why is osteoporosis so prevalent in patients with COPD? As has been shown, the use of corticosteroids alone does not account for the low BMD in these patients.

The results of Drs. Katsura and Kida suggest a relationship between low BMI and low BMD. Earlier work also supports this relationship; for example, a study published in 2000 by Incalzi et al[3] evaluated 104 consecutive patients with COPD and found that BMI was the strongest predictor of osteoporosis.

Another factor to consider is immobility. Many patients with advanced COPD have impaired functional status and mobility. Decreased activity leads to muscle weakness, which in turn can lead to falls and fractures.

Patients with chronic lung disease are often malnourished, a result of a condition known as pulmonary cachexia, which can cause low BMI. Malnutrition may also be associated with vitamin D deficiencies, and these could further jeopardize BMD.

In addition, smoking, which is quite common among COPD patients, is a well-known risk factor for osteoporosis.

CAUSE UNKNOWN BUT SCREENING RECOMMENDED

A 2002 review paper by Dr. Biskobing[4] noted that the proportion of patients with osteoporosis increases with the severity of COPD. This suggests that COPD may be an independent risk factor for decreased BMD, she said.

Although there is no consensus yet about which factors other than corticosteroid use best explain the increased risk of osteoporosis in COPD patients, researchers agree about the health problems caused by fractures. Vertebral fractures can cause back pain and decreased functional performance. Additionally, progressive kyphosis (hunched back resulting from vertebral fractures) can decrease lung volume.

Dr. Biskobing observed that evidence supports the widespread use of BMD measurements in patients with COPD. “Screening for osteoporosis should be done in all postmenopausal women with COPD. In addition, men and premenopausal women on oral corticosteroids for more than three months per year should be screened.” She also recommended screening for patients who use inhaled corticosteroids for more than three years if they also receive oral corticosteroids periodically.

Another issue is whether patients receiving corticosteroids should be given any preventive therapy. According to Dr. Biskobing, “Anyone who has been or is anticipated to be on oral corticosteroids for more than six months should be [given] an oral bisphosphonate for prevention. If bone density shows osteoporosis, then the bisphosphonate should be continued indefinitely.”

“Long-term use of a high-dose inhaled corticosteroid has been implicated in adversely affecting bone density,” Dr. Biskobing pointed out. “[However,] most studies are retrospective or short-term. To truly see the effect, a long-term (three- to five-year) study would need to be done.”

—Gale Jurasek