O7.3 Osteoporosis

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].

A large systematic review and meta-analysis to determine the fracture risk of people with COPD who were using ICS (Peng 2023) [evidence level I]. Included in the review were 44 RCTs involving 87,594 patients. Meta-analysis showed that there was a significantly increased risk of fracture risk in people with inhalers containing ICS compared to inhalers without ICS (RR, 1.19; 95% CI 1.04 to 1.37; p = 0.010), and the risk was great in people using dual bronchodilator/ICS inhalers (RR 1.30; 95% CI 1.10 to 1.53; p = 0.002) and triple therapy (RR 1.49; 95% CI, 1.03 to 2.17; p = 0.04). Other factors that were associated with increased risk, identified in subgroup analyses were treatment duration ≥ 12 months, budesonide therapy, fluticasone furoate therapy, older age, and disease severity (Peng 2023) [evidence level I]. Being aware of these findings in addition to a patient’s other risk factors for osteoporosis should underpin clinical decision-making relating to bone mineral density screening.

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.