Long-term therapy in COPD: any evidence of adverse effect on bone?

Figures & data

Figure 1 The development of bone mineral density (BMD) throughout life, factors of importance for level of BMD (genetics, sex), COPD-related factors lowering (BMD), and important factors influencing fracture risk in addition to level of BMD.

Abbreviations: IL, interleukin; TNF-α, tumor necrosis factor alpha.

Table 1 Adjusted odds ratio for fracture risk at different sites by daily dose of prednisolone in UK General Practice Research Database (GPRD) and Danish large register studies

Prednisolone daily dose	Danish register study Vestergaard et al^Citation58			GPRD study Van Staa^Citation57		GPRD study de Vries et al^Citation56
	Forearm	Hip	Spine	Hip	Spine	Hip/femur	Spine
<2.5 mg	0.99 (0.89–1.09)	0.97 (0.87–1.08)	1.16 (0.95–1.41)	0.99 (0.82–1.20)	1.55 (1.20–2.01)	1.40 (1.24–1.57)	2.89 (2.47–3.39)
2.5–7.49 mg	1.14 (0.98–1.33)	1.27 (1.11–1.44)	1.54 (1.18–1.99)	1.77 (1.55–2.02)	2.59 (2.16–3.10)
>7.5 mg	1.19 (0.99–1.43)	1.45 (1.25–1.69)	2.08 (1.54–2.79)	2.27 (1.94–2.66)	5.18 (4.25–6.31)	2.17 (1.87–2.51)	4.00 (3.29–4.86)

Notes: The Danish study comprised 124,655 subjects having sustained a fracture during the year 2000 compared to matched controls.⁵⁸ The GPRD study by van Staa comprised 244,235 oral corticosteroid (OCS) users compared to matched controls aged ≥18 years. Respiratory disease accounted for 40% of treatment indications.⁵⁷ The GPRD-study by de Vries comprised 191,752 subjects aged ≥40 years who received OCS compared to past users of CS.⁵⁶

Figure 2 Diagram showing the direct and indirect effects of glucocorticoids on bone leading to glucocorticoid-induced osteoporosis and fractures. Reproduced with permission from Canalis E, Mazziotti G, Giustina A, Bilezikian JP. Glucocorticoid-induced osteoporosis: pathophysiology and therapy. Osteoporos Int. 2007;18(10):1319–1328.¹⁴⁹ Copyright © 2007 Taylor & Francis.

Table 2 Dual energy absorptiometry measurements – recommendations

Generally Sites: hip and lumbar spine Women ≥65 years and men ≥70 years^Citation164 Younger postmenopausal women and men aged 50 to 69 years in case of one major or two minor risk factors for osteoporosis^Citation164 Ideally, all patients starting with OCS, but at least: Start of OCS with daily dose ≥5 mg for ≥3 months Need of ≥1 OCS course yearly^Citation167 Measurement interval 5 years if no risk factors or CS therapy^Citation10 2 years or more to follow loss or treatment effect 1 year if use of OCS without anti-resorptive treatment

Abbreviations: CS, corticosteroids; OCS, oral corticosteroids.

Table 3 Recommendations for prevention and treatment of osteoporosis in COPD patients

Avoid further bone loss Smoking cessation Weight-bearing and strengthening exercise Adequate nutrition Maintain weight if not overweight Rehabilitation programs in moderate to severe disease^Citation169 COPD – treatment Long-acting bronchodilators to all patients where airway obstruction might limit the level of physical activity^Citation170 ICS or ICS/LABA or long-acting anticholinergics in severe COPD in order to reduce frequency of exacerbations Reduce CS exposure by: ▪ Maintenance therapy: ICS in moderate doses ▪ Exacerbations: Consider dependent on the individual patient: Lower OCS dose (30 mg prednisolone for 7 to 8 days) High-dose ICS/LABA after one dose of prednisolone 30 mg^Citation135 Calcium and vitamin D (1200 mg and 800 IU, respectively)^Citation172 To everyone aged 50 years or more If start with OCS or high-dose ICS Bisphosphonates If daily dose of CS ≥ 5 to 7.5 mg and T-score < −1 (−1.5) If yearly cumulative dose of CS > 800 mg prednisolone If previous fragility fracture and T-score < −2.5 if no use of CS Estrogen Consider in hypogonadal premenopausal women exposed to CS PTH analogues Consider in CS users with high risk of fractures

Abbreviations: CS, corticosteroids; ICS, inhaled corticosteroids; OCS, oral corticosteroids; LABA, long-acting β2-agonist.

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