Do Patients With MS, NMOSD Have an Elevated Risk for Fractures?

Patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) have a higher risk for fractures compared with healthy individuals, according to findings from a retrospective cohort study published in Osteoporosis International.

Both MS and NMOSD are inflammatory disorders of the central nervous system that are distinguished by recurrent events involving the spinal cord, brain, and optic nerve. Individuals with MS and NMOSD often exhibit a decline in their balance and decreased bone mineral density, which are linked to a higher risk for fractures. Further, high-dose corticosteroids are frequently used in patients with MS and NMOSD, with repeated steroid use also associated with an elevated risk for fracture.

For the study, researchers conducted a large-scale nationwide cohort study, in which they sought to assess the difference in fracture risk between patients with MS and NMOSD and healthy control individuals via use of the National Health Insurance Service (NHIS) database in South Korea. Patients with MS and NMOSD were detected by using the Rare Intractable Diseases registry of South Korea and International Classification of Diseases 10th revision  (ICD-10) diagnosis codes.

Individuals with 2 or more outpatient or hospitalization claims for ICD-10 codes associated with MS or NMOSD were enrolled in the study. A total of 4981 individuals with MS and NMOSD were identified — 2515 with MS and 2466 with NMOSD. These patients had received their diagnosis between January 1, 2010 and December 31, 2017. Following exclusions for various reasons, including incomplete eligibility data, history of fracture prior to diagnosis of MS and NMOSD, or inability to match with the control population, 2546 patients were enrolled in the study — 1217 with MS and 1329 with NMOSD.

For each patient with MS and NMOSD, 5 healthy control individuals were selected. Thus, the final control group comprised 6085 matched control individuals for patients with MS and 6645 matched control individuals for patients with NMOSD. All control individuals were matched based on sex, age, and the presence of diabetes, hypertension, and dyslipidemia.

The primary study endpoint was “any newly diagnosed fracture during the study period.” Fractures were defined according to ICD-10 codes as vertebral, hip, or other fractures. Additional sites of fractures were the clavicle, the lower end of the humerus, the shaft of the humerus, the lower end of the tibia, the lower end of the radius, the lateral malleolus, and the medial malleolus. All fractures were calculated at 1-year following the date of MS and NMOSD diagnosis or the index date, since patients with these disorders are typically treated with corticosteroids within 1-year from diagnosis, thus increasing their risk for fracture.

After the index date, mean follow-up duration was 4.40 years in the group with MS and 4.08 in the group with NMOSD, compared with 4.73 years and 4.28 years in the respective control groups.

Overall, 44.2% of patients in the MS group were men and 20.7% were older than age 65. Among them, 43.5% had hypertension, 31.1% had dyslipidemia, and 16.8% had diabetes.

In the NMOSD group, 35.4% of participants were men, 15.3% were older than age 65; 30.6% had dyslipidemia, 28.1% had hypertension, and 20.7% had diabetes.

Adjusted hazard ratios (aHRs) for fractures in the MS arm vs the control arm were as follows:

• Any fractures: aHR, 1.81; 95% CI, 1.43-2.28
• Vertebral fracture: aHR, 2.06; 95% CI, 1.42-2.99
• Hip fracture: aHR, 3.36; 95% CI, 1.81-6.24
• Other fractures: aHR, 1.40; 95% CI, 0.99-1.96

The aHRs for fractures in the NMOSD arm vs the control arm were as follows:

• Any fractures: aHR, 1.85; 95% CI, 1.47-2.34
• Vertebral fracture: aHR, 2.84; 95% CI, 1.92-4.21
• Hip fracture: aHR, 3.82; 95% CI, 2.05-7.11
• Other fractures: aHR, 1.22; 95% CI, 0.87-1.70

There were no significant differences reported in the fracture incidence between the MS group and the NMOSD group.

Several limitations of this study should be noted. To begin, inaccuracies in diagnosis may exist, because all patients who were diagnosed with NMOSD after 2015 were considered NMOSD cases, not MS cases, in an effort to reduce any diagnostic error.  Additionally, the data in the present study were based on a health claims database that did not include much clinical information.

“Patients with MS/NMOSD had a 1.8-fold higher risk of fracture than matched controls, and the risk of hip fracture was especially high (3- to 4-fold higher),” the researchers noted. “Clinicians need to regularly assess patients with MS/NMOSD for the possibility of fractures and take preventative measures to reduce this risk.”

Disclosure: One of the study authors has declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of the author’s disclosures.