People with Autoimmune Diseases on Immunosuppressants Face Higher Fracture Risk

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People with an autoimmune disease who take immunosuppressants are at a higher risk for bone fractures, according to new research.1

The new retrospective study, led by Feng-Chen Kao, MD, PhD, of the school of Medicine at I-Shou University in Kaohsiung City in Taiwan, sought to find out if immunosuppressants linked to bone fractures in patients with autoimmune diseases. The investigators already knew that the risk of fractures was higher in patients with autoimmune diseases, but they were unsure if long-term usage of immunosuppressants increased the risk of the injury.

“Our findings revealed a higher risk of fracture in the immunosuppressant sub-cohort compared to the non-immunosuppressant sub-cohort in each of the four autoimmune diseases,” wrote the investigators. “These results contradict the current opinion regarding rheumatoid arthritis that considers immunosuppressant use as fracture preventative.”

Autoimmune diseases affect millions of people worldwide, and the disease tampers with a person’s quality of life.2 People with autoimmune diseases take immunosuppressants to manage their symptoms by suppressing the immune system and decreasing inflammation.1

The investigators collected data from Taiwan’s National Health Insurance Research Database, and the data included 99.9% of Taiwan’s population. They selected patients diagnosed with autoimmune diseases between 2000 - 2014, who had either psoriatic arthritis; rheumatoid arthritis; ankylosing spondylitis; or systematic lupus erythematosus. The control group did not have an autoimmune disease and were selected from the same database. The investigators matched the autoimmune disease cohort and the non-autoimmune disease cohort in a ratio of 1:4, based on age, gender, index data, and propensity scores of comorbidities.

The team examined prescription records containing dates of order, dosage, the route of every prescription, and the number of days prescribed for each drug. They measured medications between the diagnosis and 365 days later.

The team divided participants into 2 sub-cohorts, based on their use of immunosuppressants. Patients with over 30 days of immunosuppressant medication were placed in the immunosuppressant sub-cohort (n = 7277) while those who did not take any immunosuppressant medication during the 365-day window were placed in the non-immunosuppressant sub-cohort (n = 29,108). The primary outcomes were patients diagnosed with a shoulder fracture, spine fracture, wrist fracture, or hip fracture—fractures in the shoulder, spine, wrist, or hip prior to the 365 days were excluded from the study.

Overall, the risk of fractures was 1.14 times greater in patients with autoimmune diseases than for patients without the disease. The adjusted sub-distribution hazard ratio for shoulder fractures was 1.27 (95% CI, 1.01 – 1.58), for spine fractures was 1.43 (95% CI, 1.26 – 1.62) for wrist fractures was 0.95 (95% CI, 0.75 – 1.22), and for hip fractures was 1.67 (95% CI, 1.38 – 2.03).

The investigators found a high portion of patients with autoimmune disease had comorbid conditions, such as chronic lung disease, ulcers, and diabetes. The baseline distributions between the immunosuppressant sub-cohort and non-immunosuppressant sub-cohort were similar except some comorbidities, including congestive heart failure, dementia, ulcer, chronic liver disease, diabetes, and leukemia or lymphoma tumor.

The results found that the risk of hip fracture was relatively high, especially in patients with systematic lupus erythematosus who received immunosuppressant medications (95% CI, 2.17 – 5.15). Also, the incidence of hip fracture was significantly higher in the immunosuppressant sub-cohort than in the non-immunosuppressant sub-cohort.

The results of the study suggest taking immunosuppressants may increase the risk of fractures in patients with autoimmune diseases, specifically at the hip.

“Given the potential for increased fracture risk associated with the use of immunosuppressive agents, it is important for clinicians to be aware of this potential complication and take appropriate measures to mitigate the risk,” the investigators wrote. “These measures may include the close monitoring of patients, lifestyle modifications to promote bone health, and the use of bone-protective medications, such as bisphosphonates or denosumab.”

^References

1. ^{Kao F-C, Hsu Y-C, Tu Y-K, Chen T-S, Wang H-H, Lin J. Long-Term Use of Immunosuppressive Agents Increased the Risk of Fractures in Patients with Autoimmune Diseases: An 18-Year Population-Based Cohort Study. Biomedicines. 2023; 11(10):2764. https://doi.org/10.3390/biomedicines11102764}
2. ^{Wang, L.; Wang, F.S.; Gershwin, M.E. Human autoimmune diseases: A comprehensive update. J. Intern. Med. 2015, 278, 369–395. [Google Scholar] [CrossRef]}