Background/Purpose: Axial spondyloarthritis (axSpA) is associated with osteoporosis. However the underlying causes are incompletely understood. Osteoprotegerin (OPG) is a bone protective protein that acts as a decoy receptor for RANK-L and inhibits osteoclastogenesis. Previous work has suggested that antibodies to OPG (OPG-Ab) occur more commonly in patients with autoimmune disease and may be associated with increased bone turnover. The aim of this study was to determine whether OPG-Ab are associated with bone health in axSpA.

Methods: Patients with a clinical diagnosis of axSpA were recruited from routine outpatient clinics at two centres in the United Kingdom between 2011-2015. Patient demographics and disease characteristics and fracture history were recorded. All had BMD assessment using anteroposterior dual-energy X-ray absorptiometry (AP-DEXA). Serum levels of OPG-Ab were measured from each patient in triplicate using an in-house ELISA (intra-assay coefficient of variation 10.4%). Patients were considered to be positive for OPG-Ab if values were ≥13units (3 standard deviations above the mean in 100 healthy controls). Associations between OPG-Ab and disease characteristics were assessed by univariate logistic regression. Association with BMD and fractures were assessed by linear and logistic regression, respectively (adjusted for age, gender, duration since diagnosis, BMI and study centre).

Results: We studied 134 patients of whom 75% were male. The mean age was 47 (SD±15) years, and 71% were HLA-B27 positive. 16 patients tested positive for OPG-Ab (11.9%). Presence of OPG-Ab was not associated with patient demographics, axSpA disease characteristics/activity, but was associated with increasing years of disease duration (OR 1.04; 95%CI 1.00, 1.07; P=0.045). OPG-Ab positive patients had reduced hip (but not spinal) BMD and increased history of fracture (Table 1). OPG-Ab positivity was associated with reduced t-score at the hip (ß=-0.83; 95%CI -1.47,-0.18; P=0.012) and increased odds of any fracture (OR_adj4.63; 95%CI 1.36, 15.8; P=0.014).

Conclusion: This cross-sectional study demonstrates that the prevalence of OPG-Ab is much higher in axSpA than the healthy population (population prevalence 1%, P<0.001). In axSpA presence of OPG-Ab was strongly and independently associated with hip BMD and history of fractures. This raises the possibility that OPG-Ab may contribute to the bone loss and increased fracture risk observed in axSpA. Spinal BMD is not accurately assessed by AP-DEXA due to presence of syndesmophytes, and it is likely that vertebral BMD will be reduced to a similar extent at the spine. Future studies should utilize lateral spinal DEXAs. OPG-Ab positive axSpA patients may warrant more rigorous bone protection and BMD monitoring.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/autoantibodies-to-osteoprotegerin-are-independently-associated-with-low-hip-bone-mineral-density-and-increased-fractures-in-axial-spondyloarthritis/