Atopic dermatitis may increase risk for fractures
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Patients with atopic dermatitis had a higher incidence of fractures, according to a study published in Annals of Allergy, Asthma & Immunology.
Because studies have suggested that the chronic inflammation associated with atopic dermatitis (AD) may impair bone health, Teng-Li Lin, MD, of Taichung Veterans Teaching Hospital in Taichung, Taiwan, and colleagues sought to evaluate the long-term risk for fractures among patients with AD.
Researchers evaluated data from the Longitudinal Health Insurance Dataset (LHID) 2000 and LHID 2010, which are subsets of Taiwan’s National Health Insurance Research Database. The study included 36,855 patients diagnosed with AD and 147,420 control patients, with a mean age of 22.6 years and a mean follow-up time of 6.8 years for both cohorts.
Disease outcomes included fracture at any site with hospital admission or the same diagnosis at least three times. Lin and colleagues categorized the fractures as pathologic fractures or fractures of the vertebral column, pelvis, humerus, radius and ulna, femur neck, femur, tibia and fibula, or ankle.
Fractures occurred in 1,518 patients (4.12%) in the AD cohort and 5,579 (3.78%) in the reference cohort (P = .003).
The AD cohort experienced a 16-year cumulative incidence of fractures of 8.043%, which was significantly higher than the 7.366% rate observed in the reference cohort (P = .002).
Patients with AD also experienced significantly more vertebral fractures, which are the most common osteoporotic fractures, compared with the control group (0.65% vs. 0.52%; P = .004).
Patients with moderate to severe AD also had a significantly higher cumulative incidence of fractures (10.669%; P < .001). Multivariate analyses revealed that moderate to severe AD significantly increased risk for fractures (adjusted HR = 1.31; 95% CI, 1.08-1.59).
Exposure to at least 10 mg a day of systemic corticosteroids (aHR = 1.62; 95% CI, 1.38-1.91) or topical corticosteroids (aHR = 1.21; 95% CI, 1.05-1.39) also were independent risk factors, although the researchers noted that the negative effects of AD on bone health were independent of exposure to these drugs.
The researchers further found the use of disease-modifying antirheumatic drugs (aHR = 0.71; 95% CI, 0.53-0.9), which are frequently used in treating AD, and phototherapy (aHR = 0.73; 95% CI, 0.56-0.95) lowered fracture risk.
Although women are at greater risk for osteoporosis and fracture, the researchers found an association between men with AD and higher fracture risks (aHR = 1.51; 95% CI, 1.44-1.59), which they wrote may be explained by the younger AD population, as younger men often exhibit high levels of physical activity and premenopausal women have lower bone turnover rates.
Independent risk factors such as osteoporosis (aHR = 1.63; 95% CI, 1.45-1.82), postmenopausal status (aHR = 1.18; 95% CI, 1.06-1.32) and each incremental year of age (aHR = 1.01; 95% CI, 1.01-1.01) support these findings as well, the researchers wrote.
“In conclusion, the results of this nationwide matched cohort study demonstrated an increased risk of fractures in AD patients. ... It is necessary to raise awareness of the risk of fractures among people with AD,” the researchers wrote.
Perspective
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Jonathan Silverberg, MD, PhD, MPH
My colleagues and I also studied the association between AD and fractures.
Using data from the National Health Interview Survey, we found that adults with AD had higher rates of injuries and bone and joint fractures, with a peak at age 50 to 69 years. There also was a subset of adults with AD who had fatigue, sleep symptoms or mental health disturbances, with the highest odds of fractures or bone and joint injuries.
These factors are really proxy measures of more severe disease, but they also may reflect patients who have chronic sleep disturbance. Fatigue and sleepiness may be risk factors for injuries because these patients are not as alert and can be distracted. Sedating medications may have that same effect in increasing fracture risk as well.
Another study found that AD wasn’t associated with osteoporosis and osteopenia in older adults. So, it seems to be multifactorial. There is a component of sleep deprivation. There is a component of lower bone mineral density. But it’s not just that their bones are brittle. It’s that there are increased risks for injuries as well, and physical trauma is increasing those risks.
It’s not surprising that this nationwide study found increased fracture risk. Previous studies were cross-sectional, but this study looked at longitudinal data. Although there is a significant association, it’s not a massive effect, fortunately. Nevertheless, some patients do have an increased risk for fractures.
What is fascinating about this study is the association between fracture risk and topical steroids, which is a little controversial. Previous studies found mixed results. Some studies suggested there is no fracture risk from topical steroids. Systemic steroids unquestionably do increase the risk for fractures by lowering bone mineral density. Whether topical steroids present any risks is still controversial, but that’s what this study found. It is noteworthy that systemic steroids were associated with higher fracture risk than topical steroids.
Patients who were using disease-modifying antirheumatic drugs, or immunomodulators, had a lower risk for fractures. That makes sense, but we haven’t seen such data so well stated before. If the disease confers fracture risk and more severe disease confers worse risk, presumably reducing disease severity of the disease would therefore reduce fracture risk.
Of course, steroids on their own have a side effect of increasing fracture risk. In the case of those drugs that don’t negatively impact bone mineral density, we see beneficial improvements and reductions in fractures. Those are some important contributions above and beyond other studies that our group and other groups have published.
You want to use effective drugs, preferably not steroids, so you’re not having that competing effect of a medication that may on the one hand improve the disease and secondarily reduce fracture risk, but on the other hand independently increase the fracture risk. You want to use a therapy that doesn’t have an adverse impact on sleep, cognition and bone mineral density. Systemic steroids have negative impacts on all those things. That’s where this study points to unmet needs and opportunities for future drugs to address these issues.
References:
Garg NK, et al. JAMA Dermatol. 2015;doi:10.1001/jamadermatol.2014.2098.
Shaheen MS, et al. J Am Acad Dermatol. 2019;doi:10.1016/j.jaad.2018.05.026.
Garg NK, et al. Allergy Clin Immunol. 2015;doi:10.1016/j.jaci.2014.10.043.
Silverberg JI, et al. Clin Dermatol. 2017;doi:10.1016/j.clindermatol.2017.03.008.
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