A study claims a long-term prescription of glucocorticoid (GCs) could raise the risk of osteoporosis and bone fracture even in South Koreans. The researchers found the bone density dips significantly and the risk goes up high three months into the prescription.

So far, there were studies condudcted in the U.S. and Europe warning such risks, but the latest study in South Korea is a first large-scale monitoring research using epidemiologic data collected from Korean patients.

First research evaluating the correlations between glucocorticoid and fracture risk in South Korea

The 35th edition of Korean Endocrine Society’s (KES) international journal Endocrinology and Metabolism published a report on “Effects of Systemic Glucocorticoid Use on Fracture Risk: A Population-Based Study (doi.org/10.3803/EnM.2020.659)” that focused on the Korean patients.

# In the U.S. (Arthritis Care Res. 2013;65:294-8) and Europe (Rheumatology. 2011;50:1982-90), population-based studies on a long-term use of glucocorticoid have been published to raise an issue in the increasing risk of osteoporosis and bone fracture.

However, an epidemiologic data-based correlation study for patients in South Korea has never been reported before. A literature published in 2016 (PLoS One 2016;11:e0158918), by the researchers of the latest study, was the only similar kind.

Accordingly, a professor of internal medicine at University of Ulsan College of Medicine, Kim Ha Young led a group of researchers to extend the 2016 study and reviewed the relationship between epidemiologic data of population-based glucocorticoid use and risk in osteoporosis and bone fracture.

The researchers pointed out the studies on glucocorticoids published so far have been limited to oral drugs, and left ambiguity as the studies used different indicators in daily dose, cumulative amount and prescription duration.

The researchers then have decided to lessen the ambiguity by calculating the total amount of glucocorticoids prescribed based on the defined daily dose (DDD), adding all oral, parenteral and high-dose formulation of glucocorticoids, and analyzing the relationship between the total amount of systematic glucocorticoid use.

For instance, prescribing 5 mg of prednisolone, which has 10 mg of DDD, for 90 days would be calculated to 45 DDD as total amount of systematic glucocorticoid use.

Risk of bone fracture soared compared to non-user by maximum 3.28 times

The researchers randomly selected 1,896,159 patients, who had been prescribed with the drug, analyzed their cases of hip and vertebral fractures to confirm the relationship between the use glucocorticoid and risk of bone fracture.

The subjects were categorized into four groups according to total glucocorticoid DDDs: non-users (DDDs=0), low-dose users (0< DDDs ≤45), intermediate-dose users (45< DDDs ≤90), and high-dose users (90< DDDs). The study followed the groups for two years.

After two years, 3,988 out of 1,896,159 participants fractured their bone. And the risk of bone fracture was higher in glucocorticoid users with 80 cases per 10,000, whereas non-user group only had 14 cases per 10,000.

The use volume was the same as well. As glucocorticoid use increased, the cases of hip fracture also increased. And in all the groups, more vertebral fractures were noticed than hip fractures.

Excluding other factors affecting a bone fracture, the results were the same even with Cox proportional hazards model.

Compared against the non-users, the vertebral fracture risk was 1.39 times higher in the low-dose user group. Also, the intermediate-dose user group showed risk 1.94 times higher and the high-dose user group was 2.43 times higher.

The same results were apparent with the risk of hip fractures. The risk of hip fracture was 3.2 times higher in high-dose users than in non-users.

And apparently, the risk of the fractures surges from the three-month point of the prescription, and it peaks at the six-month point. The researchers explained, using the study result, the healthcare providers can predict the risk of bone fractures sustained for at least two years even after a patient stops using the drug.

Accordingly, the researchers advised the healthcare providers should project the risk of bone fractures by calculating the use of glucocorticoid for six months, based on the found evidences.

The researchers said, “The study was meaningful as it was a first large-scale research on the correlation between the use of glucocorticoid and the risk of bone fracture. In order to prevent fractures, it is necessary for the healthcare providers to evaluate the total amount of glucocorticoid prescribed to the patient and to provide appropriate treatment.”

They added, “The low-dose group did not demonstrate high surge in hip fracture risk, but the vertebral fracture risk was 1.39 times higher. As we found glucocorticoid was causing the loss in bone density, specifically in cancellous bones like vertebrae, follow-up studies are needed to seek the cut-off value in the glucocorticoid prescription.”