Patients with COPD are at increases risk for fracture due to the disease itself, the use of high dose corticosteroids and coexisting risk factors such as hypogonadism (induced by corticosteroid 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 systematic review of 58 studies of heterogeneous quality limited by largely cross-sectional designs (8,753 patients with COPD) found a mean prevalence of 38% (95% CI 34 to 43) for osteoporosis in patients with COPD, with increasing odds ratios for osteoporosis associated with lower BMI and sarcopenia (Chen 2019), indicating that people with COPD are at special risk of osteoporotic fracture. The overall OR for osteoporosis in COPD was 2.83 (95% CI: 2.00 to 4.03), with particular risk (OR 4.26: 95% CI: 1.07 to 16.99) for those with BMI of < 18.5 kg/m2. Although there is conflicting evidence as to the strength of a causative relationship, oral or inhaled high dose corticosteroids, coexisting risk factors such as hypogonadism (induced by corticosteroid therapy itself in high doses in men and women), physical inactivity, repeated periods of immobilisation from hospital admissions, and low dairy food intake may be potential contributory risk factors. Assessment of vitamin D status, and other risk factors such as coexisting illnesses that may influence the skeleton (e.g. primary hyperparathyroidism) may also be required, with bone densitometry to investigate further.
Patients with vertebral compression fractures, visualised on a lateral chest x-ray, have been demonstrated to have more frequent admissions, longer length of hospital stay, and increased mortality in the two years after admission (Pascual-Guardia 2017) [evidence level III-2]. A meta-analysis by Kakoullis et al (2021) included 27 studies with a range of study designs, with 7662 participants and defined osteoporosis as a T-score of -2.5 SD where available. Participants with osteoporosis and or vertebral compression fractures were found to be older (3.17 years, 95% CI 2.14-4.19), lower BMI -3.15 (95% CI -4.41–1.88) and more likely to be female, which are recognised general population risk factors. These participants had a mortality OR of 2.40 (95% CI 1.24-4.64) and lower FEV1 -0.41L (95% CI -0.59- -0.24) with a lower FEV1/FVC ratio. The authors note that it is likely that osteoporosis is a marker of severity of COPD or patient frailty, with surrogate associations with the outcomes demonstrated, rather than a direct cause of increased airflow obstruction or death. Pro-active screening and preventative treatment of osteoporosis are recommended (Kakoullis 2021) [evidence level I].
There are contradictory findings of a small but deleterious effect of inhaled corticosteroids at conventional doses on fracture risk. Triamcinolone was associated with reduced BMD in the Lung Health Study (Lung Health Study Research Group 2000) [evidence level II]. However a separate study by Ferguson et al (Ferguson 2009) demonstrated that the combination of salmeterol and fluticasone 1000 micrograms daily had no increase in decline in bone mineral density over three years in compared with placebo in the subgroup of patients whose bone density was measured [evidence level II].
Guidelines on the currently recommended screening, prevention and treatments of osteoporosis, including corticosteroid-induced osteoporosis are available elsewhere including the eTG guidelines on Osteoporosis and minimal trauma fractures.
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