ICS, OCS use in asthma may carry bone health risks

Patients with asthma who are treated with inhaled or oral corticosteroids may have an elevated risk of osteoporosis or fragility fracture, according to a study from the UK.

“Our findings provide evidence that both [oral corticosteroid (OCS) and inhaled corticosteroid (ICS)] exposure have deleterious effects on bone health,” said the researchers of the two nested case-control studies.

“The use of OCS and ICS should be kept to the minimum necessary to treat symptoms and should be stepped down if symptoms and exacerbations are well managed,” they said.

The researchers used linked data from the Clinical Practice Research Datalink and Hospital Episode Statistics databases to identify adults diagnosed with asthma between April 2004 and December 2017 who had also been diagnosed with osteoporosis (n=1,564) or experienced fragility fractures* (n=2,131). They were each age- and gender-matched with ≤4 patients with asthma from the same general practice with no documented osteoporosis (n=3,313) or fragility fractures (n=4,421).

Information on corticosteroid use, number of prescriptions filled, and cumulative dose in the year prior to osteoporosis or fragility fracture was documented.

Compared with no OCS prescriptions, a greater number of OCS prescriptions in the year prior to osteoporosis was associated with a higher risk of osteoporosis (adjusted odds ratios [adjORs], 1.12, 1.34, 3.80, and 4.50 for 1, 2–3, 4–8, and ≥9 prescriptions). A greater cumulative dose of OCS was also associated with a higher risk of osteoporosis (adjORs, 1.21, 2.05, 4.04, and 4.79 for ≤500, 501–1,000, 1,001–2,500, and >2,500 mg, respectively). [Thorax 2020;doi:10.1136/thoraxjnl-2020-215664]

Greater ICS use was also associated with an increased risk of osteoporosis, but to a lesser extent than the association with OCS (adjORs, 1.35, 1.51, and 1.60 for 1–6, 7–10, and ≥11 prescriptions, respectively). A similar finding was noted with greater cumulative ICS dose (adjORs, 1.18, 1.26, 1.50, and 1.63 for ≤40, 41–80, 81–120, and >120 mg, respectively). The effect was comparable across ICS types, with the highest risk noted with budesonide (adjOR, 1.56).

Increasing number of OCS prescriptions was also associated with an increased risk of fragility fracture (adjORs, 1.11, 1.24, 1.31, and 2.16 for 1, 2–3, 4–8, and ≥9 prescriptions, respectively, compared with no prescriptions), as was greater cumulative OCS exposure (adjORs, 1.11, 1.20, 1.54, and 1.99 for ≤500, 501–1,000, 1,001–2,500, and >2,500 mg, respectively).

Similarly, increasing number of ICS prescriptions was also associated with an increased risk of fragility fracture (adjORs, 1.02, 1.24, and 1.31 for 1–6, 7–10, and ≥11 prescriptions, respectively), as was greater cumulative ICS dose (adjORs, 0.94, 1.13, 1.14, and 1.20 for ≤40, 41–80, 81–120, and >120 mg, respectively).

In the year prior to osteoporosis or fragility fracture, 31.4 and 21.4 percent of OCS users had prescriptions for bisphosphonates, as did 33.8 and 19.4 percent of ICS users.

“We found a clear dose-response relationship, with higher cumulative doses and number of OCS and ICS prescriptions being associated with increased odds of osteoporosis and fragility fracture,” said the researchers. The association between the number of prescriptions, which suggests intermittent vs regular use, and risk of negative bone outcomes suggests that short-term OCS use may have a deleterious effect, they added.

They also highlighted the low number of bisphosphonate prescriptions among OCS users. “Current guidelines on asthma do not cover the management of bone comorbidities in detail,” they said. “Our results suggest that risk and prevention of osteoporosis and fragility fractures should be addressed explicitly in future guideline updates … bisphosphonate comedication should be considered according to guidelines for bone protection,” they said.