Researchers combine nanobiotechnology, neutrophils and nucleic acid to combat lupus
“We already know that patients with lupus have altered bone metabolism and are at risk of osteoporosis,” says Stacy Ardoin, MD, a rheumatologist at the Ohio State Wexner Medical Center, chair of Pediatric Rheumatology and director of the Lupus Clinic at Nationwide Children’s Hospital. “What we hoped to characterize with our study was the relationships between vitamin D levels, lupus activity and markers of bone turnover.”
A team of Ohio State researchers, including Dr. Ardoin, used the clinical registry and biorepository data of 42 patients with systemic lupus erythematosus (SLE) to analyze serum samples for osteocalcin as a marker of bone formation, C-terminal telopeptide of type 1 collagen (CTX) as a marker for bone resorption and 25-hydroxy vitamin D.
The Ohio State researchers found that patients with an SLE Disease Activity Index 2000 (SLEDAI) score of 3 or greater had a lower median osteocalcin level, as well as lower 25-hydroxy vitamin D levels in comparison to patients with a SLEDAI score less than 3.
However, no significant differences in bone turnover markers were observed between patients dichotomized into subgroups using a 25-hydroxy vitamin D cut-off of 30 ng/mL or by a daily prednisone dose greater than 5 mg or less. The team also confirmed that osteocalcin levels were negatively correlated with SLEDAI scores (P = 0.034) and were positively correlated with the CTX index (a ratio of measured CTX value to the upper limit of the normal value for age and gender) (P < 0.01). No association between the CTX index and SLEDAI scores was found.
“Ultimately, we concluded that SLE disease activity and its treatment may have direct effects on markers of bone formation, but we didn’t see a relationship with markers of bone resorption in this cohort of established SLE patients,” Dr. Ardoin says. The researchers suspect that this likely is due to the inflammation-suppressing effects of glucocorticoids, which inhibits cytokine-induced osteoclast activity.
“Our findings reinforce the fact that there is a fine balance between disease control and the use of glucocorticoids with regard to bone health, so working to optimize bone health in lupus is very important. While we don’t have randomized controlled trials (RCT) data specific for fracture-reduction risk in lupus, we can extrapolate for the existing literature that it is beneficial to optimize vitamin D and calcium intake and use preventive or therapeutic doses of anti-resorptive of other osteoporosis medications where appropriate,” Dr. Ardoin says. She explains that this approach is only reinforced by recent RCT data from the VITAL trial that shows prescribing patients 2000 IU of vitamin D daily may lead to a 22% reduction in the development of autoimmune diseases, which would include SLE.
“We have a very high patient participation rate in our registry and biorepository — well over 50% — because our patients understand the importance of our research and know the potential benefit, either for themselves or future lupus patients,” she says.
“I’m confident we’re headed in the right direction, and the generosity of these patients will give our research team a notable advantage as our division continues to explore how vitamin D mitigates SLE — and potentially so many other diseases as well.”
