ATLANTA--The risk of osteoporosis is markedly higher in men with chronic lung disease than in men without such disease, and corticosteroid use is not the only culprit--lung disease itself appears to confer a marked increase in risk. New research indicates that men with chronic lung disease who use long-term corticosteroid therapy face a ninefold rise in the risk of osteoporosis; among those who do not use corticosteroids, that risk is increased fivefold.[1] Furthermore, inhaled corticosteroids appear to have almost as deleterious an effect on bone mass as oral agents have.

Although many factors are known to contribute to bone loss in postmenopausal women, osteoporosis in men is less well understood. In particular, the relationship between chronic lung disease and osteoporosis in men, and the extent to which long-term corticosteroid therapy increases the risk of bone loss in this population, have not been well studied. To address this problem, investigators from the Emory University School of Medicine assessed the role of clinical and biochemical variables in men with chronic lung disease.

Iqbal and colleagues[1] found a surprisingly high increase in the risk of osteoporosis. Men with chronic lung disease have an almost identical burden of disease as do postmenopausal women age 60 to 90 years, for whom the prevalence of osteoporosis has been estimated to be 30%, these investigators noted. "It would be prudent to consider men with chronic lung disease for bone densitometry screening even if they are not treated with corticosteroids," they added.

These investigators conducted a cross-sectional medical survey of 171 men (age 23 to 90 years) with chronic lung disease who were treated with oral, inhaled, or no corticosteroid therapy. A control group of men without lung disease was recruited from the same clinic population. All study subjects underwent bone density measurement of the spine and left hip. Osteoporosis was defined as a T score of less than -2.5 at either site, based on criteria from the World Health Organization.

All of the men with chronic lung disease lost bone mass, regardless of whether they were taking corticosteroids--which indicates that lung disease is an independent risk factor for osteoporosis. Overall, subjects with chronic lung disease were five times more likely than controls to meet the criteria for osteoporosis, the researchers found.

Although the risk of osteoporosis was greater in those who used long-term corticosteroid therapy than in those who did not use such therapy, "the proportion of subjects with osteoporosis or osteopenia did not differ between groups treated with oral or inhaled corticosteroids, suggesting that chronic use of inhaled corticosteroids appeared to offer no protection from steroid-induced bone loss," according to Iqbal and colleagues. Findings from previous studies had suggested that oral corticosteroids are more likely than inhaled corticosteroids to cause osteoporosis.

Among male patients with chronic lung disease who had not been treated with corticosteroids, the reduction in bone mass was relatively greater at the hip than at the spine. Iqbal and colleagues suggested that "patients with chronic lung disease may be at a greater risk for bone loss at the hip, in part because of decreased ambulation and loading at this site." In this study, all of the subjects with chronic lung disease reported a decreased level of exercise, in comparison with the control subjects.

Several other clinical and biochemical variables were measured to determine whether they correlated with bone mass. But of these, only body mass index (BMI) was found to be an independent predictor of bone mass. In the subjects with the lowest bone mass, BMI was often below the normal median value, and "this may indicate that the loss of bone mass from chronic lung disease occurs once the disease is severe enough to cause weight loss," said the investigators. Thus, patients with a low BMI may be at particularly high risk for osteoporotic fractures.

Other researchers have suggested that specialists and generalists alike fail to recognize asymptomatic bone loss in high-risk patients with lung disease, thus missing the opportunity to prevent, slow, or reverse osteoporosis. Half or more of all patients with chronic lung disease may have osteopenia or osteoporosis, according to Marc F. Goldstein, MD, who is from the Asthma Center in Philadelphia. Although long-term corticosteroid therapy undoubtedly increases the risk of osteoporosis, it remains "instrumental in decreasing morbidity and mortality in patients with chronic lung disease," he said.

Goldstein and colleagues[2] suggested several strategies to reduce the prevalence of corticosteroid-induced bone loss in patients with chronic lung disease (both obstructive disease and asthma). These strategies include:

• Appropriate use of nonsteroidal anti-inflammatory therapy to limit exposure to corticosteroid therapy.
• Understanding the adverse effects of chronic oral and inhaled corticosteroid therapy.
• Early evaluation of patients with asthma and chronic obstructive pulmonary disease to identify those in whom bone loss is developing. This should include measurements of bone mineral density in the lumbar spine or femoral neck, as well as standard lateral thoracic and lumbar spine radiographs.

In addition, Goldstein and colleagues recommend that patients with normal T scores and no spinal fractures should be given calcium and vitamin D to impede the progression of osteopenia. (If hypercalciuria develops, a calcium-sparing diuretic can also be given.) For those patients who show evidence of bone loss or spinal fractures, it may be reasonable to add a bisphosphonate or calcitonin to the calcium and vitamin D supplementation, they added. (Note, however, that these drugs have been studied predominantly in postmenopausal women, and thus, their long-term safety in men or younger women has not been established.) Hormone replacement therapy can also be considered for postmenopausal women. Bone mineral density should be reassessed every 12 months to check for ongoing bone loss.

--Margaret A. Inman

References
1. Iqbal F, Michaelson J, Thaler L, et al. Declining bone mass in men with chronic pulmonary disease: contribution of glucocorticoid treatment, body mass index, and gonadal function. Chest. 1999;116:1616-1624.
2. Goldstein MF, Fallon JJ Jr, Harning R. Chronic glucocorticoid therapy-induced osteoporosis in patients with obstructive lung disease. Chest. 1999;116:1733-1749.