ACPA Positivity May Not Align with Osteoporosis Risk

Positive ACPA status may not necessarily mean a greater likelihood of osteoporosis and fracture for rheumatoid arthritis patients, study shows.

ACPA positive patients being treated for rheumatoid arthritis do not have a greater prevalence of osteoporosis and fragility fractures compared with ACPA negative patients, according to the results of a real-world study presented by researchers at the annual meeting of the American College of Rheumatology.

Edgar Wiebe, of the Departments of Rheumatology and Clinical Immunology, Charité University Medicine Berlin, Germany, said the results were surprising because ACPA positivity in rheumatoid arthritis is clearly associated with a more severe course of the disease, especially in terms of local bone loss and higher inflammatory activity. This is backed up by the pathophysiological explanations for these observations and several studies associating ACPA and/or rheumatoid factor positivity with negative effects on systemic bone.

However most previous studies looking at the impact of ACPA status on bone have focused on patients with recent RA onset, did not fully account for other all bone-influencing factors or were retrospective. Wiebe and colleagues took a different approach, enrolling a real-life cohort with a longer disease duration and documenting known and potentially unknown factors prospectively.

“We applied a cross-sectional, matched-pair analysis in order to compare the differences between ACPA positive and ACPA negative patients in factors that influence bone health, i.e. we aimed not at identifying primarily predictive factors but rather aimed a looking how both groups differ. This also allowed us to compare aspects of disease management and whether there is a difference in real life. Thus, we applied a somewhat different approach,” Dr. Wiebe explained.

They matched 114 ACPA positive to 114 ACPA negative rheumatoid arthritis patients from the Rh-GIOP study by age, sex, and body mass index. The Rh-GIOP study is an ongoing prospective observational study collecting and analyzing disease- and bone-related data from patients with chronic rheumatic diseases or psoriasis treated with glucocorticoids. 

Descriptive analyses were performed on the patient data, with values displayed as mean ± standard deviation for continuous variables, and non-parametric tests were used at a two-sided significance level of 5% to compare differences in underlying and potential risk factors.

The results showed that APCA positive patients had a significantly longer mean disease duration (13.9 vs 9.9 years, p< 0.001), higher mean cumulative glucocorticoid dose (22.3 vs 13.2g, p< 0.01) and mean duration of glucocorticoid therapy (10.1 vs 6.6 years, p< 0.01). However, there was no significant difference in the prevalence of osteoporosis assessed by dual-energy X-ray absorptiometry (DXA) (18.4 vs 20.2%), or in the prevalence of vertebral (7.0 vs 5.3%) or non-vertebral fractures (31.6 vs 29.8%).

C-reactive protein levels as a marker of disease activity were significantly higher in ACPA positive patients (mean: 8.8 vs 4.3mg/l, p= 0.02), while mean disease activity score (DAS)28 levels were slightly lower (2.4 vs 2.7, p= 0.05). No difference in health assessment questionnaire (HAQ) was found.

RA-specific treatments were similar, including current daily glucocorticoid dose, apart from rituximab and targeted synthetic disease modifying anti-rheumatic drugs which were more frequently used in ACPA positive patients; the proportions of patients using the drugs were 9.6 vs 2.6% (p=0.0)5 and 5.3 vs 0% (p=0.029) respectively.

There were no significant differences between ACPA positive and ACPA patients in anti-osteoporotic treatment, prevalence of comorbidities or concomitant medication, and bone-specific laboratory parameters.

“As we put much effort in considering and documenting all potentially influencing factors, we were surprised that there was no other factor that would explain why ACPA negative rheumatoid arthritis patients seem to have a very similar outcome in bone health parameters. This is somewhat remarkable, indeed,” Wiebe said.

Asked to hypothesize on the possible reason, Dr. Wiebe suggested: “Optimal management of disease activity with or without glucocorticoid may represent a mainstay in preventing disease-related comorbidities such as osteoporosis. Assuming ACPA positivity is in fact a major contributor for systemic bone loss, then the comparatively longer treatment with glucocorticoids in this group might have prevented more severe bone loss."

"Alternatively, it might also be that ACPA negativity just needs to be considered an equally severe entity of rheumatoid arthritis and must not be underestimated when choosing the right treatment," Dr. Wiebe said.

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REFERENCE

ABSTRACT 0132. “Prevalence of Osteoporosis and Fragility Fractures Is Not Different Between ACPA Positive Patients Compared to ACPA Negative Patients in a Real World Setting, Despite Longer Disease Duration and Glucocorticoid-Treatment.” The annual meeting of the American College of Rheumatology. 9:00 AM, Friday, Nov. 6, 2020.