Two Bone Metabolism-related Proteins May Help Determine Ankylosing Spondylitis Risk, Study Suggests

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by Alice Melao |

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Determining blood levels of two proteins — osteoprotegerin (OPG) and receptor activator of nuclear factor-kB ligand (RANKL) — may help identify patients at risk of having ankylosing spondylitis, a review study suggests.

However, these potential biomarkers should be used carefully as they could be influenced by race, inflammatory factors, and disease activity, the researchers said.

The study, “Serum Levels of OPG, RANKL, and RANKL/OPG Ratio in Patients with Ankylosing Spondylitis: A Systematic Review and Meta-analysis,” was published in Immunological Investigations.

Ankylosing spondylitis is an immune-mediated inflammatory autoimmune arthritis that most commonly affects adults. It is characterized by damage to the spine bones, hip joints, and spine attachment points, which can lead to loss of joint function and painful disability.

The underlying mechanism involved in ankylosing spondylitis remains elusive, but bone loss and growth have been reported to be relevant contributors to the disease’s development. Due to this, biomarkers of bone metabolism have gained researchers’ attention as potential biomarkers to monitor and predict the outcomes of this rare disease.

OPG and RANKL are important regulators of bone metabolism. Imbalances in the levels of these two proteins have been directly linked to several diseases that are characterized by bone remodeling, including rheumatoid arthritis and chronic arthritis. However, until now, studies assessing these proteins in ankylosing spondylitis have failed to provide conclusive information on their potential role in the disease.

Researchers at Anhui Medical University in China reviewed the clinical data available from 20 published studies to gain a more detailed and broader perspective of the contribution of OPG and RANKL to ankylosing spondylitis progression.

Pooled data included information from a total of 1,592 patients with ankylosing spondylitis and 1,064 healthy volunteers without the disease.

Blood levels of OPG and RANKL, as well as the RANKL/OPG ratio (an important determinant of bone mass and skeletal integrity), were significantly higher in ankylosing spondylitis patients than in the control group.

High OPG blood levels might inadequately inhibit bone resorption, which could help explain the presence of excessive ossification — formation of new bone material — in ankylosing spondylitis patients. In contrast, high RANKL levels may explain the high incidence of osteoporosis (bone mass loss) during the early stages of the disease.

“Radiographic damage in early stage of AS is initially characterized by erosive changes followed by a distinct … skeletal response, which results in excessive bone formation,” the researchers wrote. “Accordingly, early stage of AS [is] prone to osteoporosis while AS with long disease duration [is] prone to paravertebral syndesmophytes [excessive ossification].”

These findings are further supported by the altered RANKL/OPG ratio, which denotes an imbalance in bone metabolism in this patient population.

Further analysis revealed that the levels of these two proteins were directly affected by race, inflammatory factors, and disease activity. Asian patients and those with high erythrocyte (red blood cells) sedimentation rate (ESR) had higher levels of OPG than healthy volunteers.

Patients of Asian origin and those with C-reactive protein (CRP) higher than 10 mg/L (a marker of inflammation), ESR higher than 20 mm/h, disease duration of eight or fewer years, or a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) disease scores higher than four points (higher disease activity) also had higher blood RANKL levels than controls.

“We hypothesized that serum OPG and RANKL levels may be used as potential biomarkers to reflect inflammation and bone metabolism in ankylosing spondylitis,” the researchers wrote. “But they could be influenced by race, inflammatory factors, and disease activity of ankylosing spondylitis patients.”