Asthma Inhalers May Be Linked to Increased Risk of Osteoporosis

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Use of either oral or inhaled corticosteroids to manage asthma can increase the risk of osteoporosis and fragility fractures, suggest the findings of a large study published in Thorax.

Previous studies looking at the impact of asthma medications containing corticosteroids on bone health have produced conflicting results. To try to get a clearer picture, researchers at Nottingham University in the UK assessed the impact of dosage, number of prescriptions filled and type corticosteroid used on osteoporosis and fragility fractures.

Previous studies had focused on the impact of asthma medication on bone mineral density, explained Christos Chalitsios, Division of Respiratory Medicine at School of Medicine, University of Nottingham, Nottingham, UK.

“Bone mineral density can be a less sensitive predictor of fractures, and fractures can occur at higher bone mineral density levels. So, the quantification of the risk of osteoporosis and fragility fracture due to corticosteroids in our study can provide pragmatic guidance to clinicians by stratifying bone health risk by dose, number of prescriptions, and type of oral corticosteroid and inhaled corticosteroid.”

Using data from the Clinical Practice Research Datalink (CPRD) GOLD database, which contains anonymised health records for 15.4 million patients in the UK, and Hospital Episode Statistics (HES), which record all hospital admissions in England, the researchers identified all adults with asthma diagnosed between April 2004 and December 2017, who also had either a diagnosis of osteoporosis or experienced a fragility fracture. These patients were matched with at least four patients of the same age and gender from the same general practice who did not have osteoporosis or fragility fractures.

The number of prescriptions filled and dosage was used to work out the amount and duration of steroid treatment for the 12 months leading up to a diagnosis of osteoporosis or fragility fracture.

There was a clear association between both cumulative dose and number of courses of inhaled or corticosteroid tablets and the risk of osteoporosis or fragility fractures.

Two to three steroid tablet prescriptions in the preceding 12 months were linked with a larger risk of osteoporosis, and the risk increased with greater corticosteroid exposure. After adjusting for confounding factors such as such as smoking, weight, and alcohol intake, patients who received nine or more prescriptions for oral corticosteroids containing a cumulative doses of 2500 mg or more had a 4.5 times greater risk of osteoporosis than patients who did not receive the drugs and more than twice the risk of fragility fracture.

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The risks were lower for use of inhaled corticosteroids but still significant. Patients who had received at least eleven prescriptions of inhaled corticosteroids had a 60% increased risk of osteoporosis and a 31% increased risk of fragility fracture. Again, the risks increased with increases in the cumulative dose of inhaled corticosteroid, with patients who received cumulative doses of more than 120 mg in the preceding year 20% more likely to sustain a fragility fracture.

Just half of patients prescribed corticosteroid tablets and even fewer prescribed corticosteroid inhalers (48%) were also prescribed bisphosphonates in the year before receiving their diagnosis of osteoporosis or fragility fracture.

The researchers concluded that both oral and inhaled steroids are associated with an increased risk of osteoporosis and fragility fracture in people with asthma and that the use of these drugs should be kept to the minimum necessary to treat symptoms and should be stepped down if symptoms and exacerbations are well managed.

“Our study suggests steroid administration at the lowest possible level to maintain asthma control. Nevertheless, it should be noted that the patients should not stop receiving their inhalers, as they save lives. Clinicians should also consider bone protection guidelines,” said Chalitsios said.

“For the time being, there is no asthma specific bone protection guidelines,” he added. “In our view, it is important the risk and prevention of osteoporosis and fragility fracture to be addressed explicitly in future asthma guideline updates.”

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REFERENCE

Chalitsios CV, Shaw DE, McKeever TM. "Risk of osteoporosis and fragility fractures in asthma due to oral and inhaled corticosteroids: two population-based nested case-control studies." Thorax doi: 10.1136/thoraxjnl-2020-215664