Inhaled steroids (like fluticasone, beclomethasone, and budesonide) and oral steroids (like prednisone and methylprednisolone) are standard therapies for asthma management and flare-ups, particularly for people with severe asthma.
Though doctors and health organizations, including the Asthma and Allergy Foundation of America and the American Lung Association, have long recognized that weakening bones and osteoporosis can be long-term risks associated with taking these medications, recommendations on managing this risk in patients with asthma are not well-established.
“We believe that a lack of large-scale evidence on bone risk in asthma has so far meant that official guidance has neglected to cover it,” says Christos Chalitsios, a PhD student in respiratory medicine at the University of Nottingham School of Medicine in the United Kingdom.
He is the lead author of new research published online in October in the journal Thorax that Chalitsios says he and his colleagues hope will help in the development of more precise guidelines for managing bone health risks in patients on steroid medications (also sometimes referred to as corticosteroids).
The new data show a link between both cumulative dose and number of courses of inhaled or steroid pills and the risk of osteoporosis or fragility fractures.
“Our study suggests risk and prevention of osteoporosis and fragility fractures should be addressed explicitly in future guideline updates,” Chalitsios says.
Data Shows Steroid Drugs Increase Bone Health Risks Among People With Asthma
For the new study, the researchers drew on anonymized health records of 69,074 patients with asthma living in the United Kingdom.
They specifically looked at 1,564 patients with osteoporosis; a control group of 3,313 patients without osteoporosis matched for age, gender, and the practice in which they were treated; 2,131 patients with fractures; and 4,421 patients without fractures, also matched for age, gender, and practice.
Chalitsios and his colleagues examined the impact of oral and inhaled steroids on osteoporosis and fracture in two smaller populations of people with asthma. By looking at these smaller cohorts, the researchers were able to control for other factors likely to affect bone health, including smoking, weight, and alcohol intake.
Bone Health Risks Linked to Oral Steroids
In comparing 992 people with osteoporosis to 2,607 without, the individuals taking two to three oral steroid prescriptions in a 12-month period were about 1.34 times (34 percent) more likely to have osteoporosis than those not taking any oral steroids.
The risk grew substantially for those who took nine or more prescriptions (adding up to cumulative doses of 2,500 milligrams [mg] or more of the drugs). These individuals were four times (400 percent) more likely to be diagnosed with osteoporosis compared with those who weren’t prescribed these oral drugs.
The scientists also looked at a subgroup of 1,663 who had fractures and compared them with 3,676 people who did not have fractures. Those on oral steroids were twice as likely to have had a fracture.
Bone Health Risks Linked to Inhaled Steroids
Inhaled steroid drug use also ratcheted up the risk of osteoporosis diagnosis compared with no steroid drug use, though it was not as heightened as for oral drugs.
Asthma patients given 11 or more prescriptions for inhaled steroids within 12 months were 1.6 times (60 percent) more likely to have osteoporosis and 1.31 times (31 percent) more likely to have had a fracture compared with those not prescribed these drugs.
Individuals on inhaled steroids were 20 percent more likely to sustain a fragility fracture than those not taking inhaled steroids if their doses added up to more than 120 mg in a year.
The researchers noted in the study that patients with asthma and both osteoporosis and fracture were more likely to smoke, had more comorbid illness, and were of a lower socioeconomic status compared with the individuals who served as the controls.
Many Are Not Taking Bone-Bolstering Supplements
Approximately half of patients taking oral steroid drugs and fewer than half of those taking inhaled steroids were prescribed bisphosphonates in the year leading up to a diagnosis of osteoporosis or fracture, according to the new data. The scientists called the low percentage of bisphosphonate use (which could help prevent a bone problem) disappointing.
“Bisphosphonates are the most effective bone protection therapy, and they are recommended for those people who are receiving long-term or high doses of [oral steroids],” says Chalitsios.
It’s important to point out that the researchers looked at existing records of patients’ steroid drug use and bone incidents. Because the data was observational, the analysis does not necessarily prove that the drug use did or didn’t cause the bone problems — only that they were related.
The study authors also highlight that inhalers can be difficult to use correctly, so actual doses taken may have been overestimated. The analysis also tracked prescriptions filled versus actual use, another way medication use may have been overestimated.
Albert Rizzo, MD, the chief medical officer of the American Lung Association and the chief of the pulmonary and critical care medicine section at Christiana Care Health System in Newark, Delaware, says it’s difficult to get a grasp on what an average amount of cumulative inhaled steroid is over a year’s time.
“Patients are placed on varying doses, high to low — some take them once or twice daily, and compliance on that regimen is always an issue,” Dr. Rizzo says. “There is also the fact that not all inhaled steroids represent the same molecule but a range of molecules that have slight differences in potency.”
It’s important to note that people with asthma rely on inhaled steroids as a first-line emergency controller medicine when symptoms flare up. Those with more severe persistent asthma may take oral steroids to keep their condition under control. These drugs have an anti-inflammatory effect that can reduce inflammation and ease breathing.
For many asthma patients, these drugs can be lifesavers, and Chalitsios and his colleagues stress that patients should continue taking these medications as prescribed despite potential side effects. “Patients with asthma should not stop taking their inhalers. They save lives,” Chalitsios says.
The takeaway message here is that these risks should be better managed as part of standard asthma care, he says.
Data Are a Wake-Up Call to Pay More Attention to Bone Health for Patients on Steroids
For Rizzo, the article spotlights the fact that currently there are no set guidelines as to how often bone density tests should be done and when drugs like bisphosphonates should be taken.
“I think an important aspect of that article is that it again raises awareness that osteoporosis and osteopenia [a condition of lower bone density] can be side effects of being on corticosteroids,” he says.
Inhaled steroids, which are delivered directly to the lungs, require smaller doses than oral steroids and tend to have fewer side effects, Rizzo says. But the new data suggest inhaled steroids can pose significant risks, too.
“The research is also a wake-up call to say let's monitor the bone density a little more frequently in this population, and have some better criteria about when to use drugs like this in patients,” Rizzo says.
That said, Rizzo was not surprised by the results, because previous research has already suggested that even inhaled steroids may lead to an imbalance in the body that causes bone loss and deterioration of bone architecture, and osteoporosis and osteopenia are certainly recognized adverse events from steroids.
“The point is we ought to be doing a better job in monitoring the situation with regard to bone resorption [a complex biological process that can result in shrinkage or loss of bone] and osteoporosis, especially in patients on long-term critical steroids,” he says.
The Bottom Line for People With Asthma: Continue Taking Prescribed Drugs — if You’re on a Steroid, Consider Talking to Your Doc About Bone Health
The message to clinicians prescribing these medications to people with asthma is to step down medication dose if symptoms and exacerbations are well managed. Doing so could make a difference in reducing the risk of these side effects.
In the research, investigators lay out guidance for clinicians by stratifying bone health risk by dose, number of prescriptions, and type of oral corticosteroid and inhaled corticosteroid.
The hope is that the data can help inform better bone protection guidelines for people with asthma, Chalitsios says.
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