Patients with COPD are at increases risk for fracture due to the disease itself, the use of high dose glucocorticoids and coexisting risk factors such as hypogonadism (induced by glucocorticoid therapy itself in high doses in men and women), immobilisation reduced muscle mass and other factors. These patients may have reduced bonemineral density (BMD) due to a reduction in bone formation and perhaps increased bone resorbtion, the latter being primarily due to the underlying disease itself. A recent systematic review by Graat-Verboom (Graat-Verboom et al., 2009) described an overall mean prevelance of osteoporosis of 35.1% (range 9 - 69%) with increasing odds ratios for osteoporosis associated with FEV1, lower BMI and lower fat free mass index.
Although there is little evidence of a deleterious effect of inhaled glucocorticoid at conventional doses (<2, 200 mcg/day) on fracture risk triamcinolone was associated with reduced BMD in the Lung Health Study (Lung Health Study Research Group, 2000) [evidence level II]. In a large study by Ferguson et al(Ferguson et al., 2009) comparing the effects of salmeterol, fluticasone 1000 micrograms daily, the combination, or placebo, there was no increase in decline in bone mineral density over three years in active arms compared with placebo in the subgroup of patients whose bone density was measured [evidence level II]. Australian Guidelines on the prevention and treatment of osteoporosis, including glucocorticoid-induced osteoporosis have been published. (Sambrook et al., 2002) Information on the current subsidies relevant to these drugs can be found at http://www.osteoporosis.org.au/health_rebates.php, or on the website of the Pharmaeceutical Benefits Scheme (www.pbs.gov.au) Higher doses of inhaled glucocorticoids are associated with suppresses biochemical markers of remodelling but data on BMD and fractures at these doses are not available (Jones et al., 2002) [evidence level I].
Despite lack of evidence, management strategies in individuals taking long term glucocorticoid therapy should include investigation of fracture risk including bone densitometry, assessment of vitamin D status, and other risk factors such as coexisting illness that may influence the skeleton (e.g. primary hyperparathyroidism). In individuals with low BMD at onset and in those taking more then 10-15mg of prednisolone per day or who have several risk factors for osteoporosis and whose BMD is <1.5 standard deviations below the young adult mean, treatment should be considered.
Evidence for fracture risk reduction is available for alendronate, risedronate, etidronate and parathyroid hormone. There is no evidence that calcitriol reduces fracture risk and some evidence to the contrary, so that the use of this drug is not recommended (Homik et al., 2000) However, most patients in these studies did not have respiratory disease. Although calcium supplementation has not been demonstrated to reduce the risk of fracture in osteoporosis, a reduction in remodelling rate with some possible benefit in slowing bone loss is possible so calcium supplements are appropriate. Any deficiency of vitamin D should be corrected with supplements.
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COPD-X Plan - Version 2.32 - June 2012