Session Type: Abstract Submissions (ACR)
Background/Purpose: Generalized bone loss (osteoporosis or osteopenia) is more common in patients with rheumatoid arthritis (RA) than in the general population. Recent studies suggest that inflammation in RA is a main contributor to this form of bone loss. Inflammation is mediated in turn by multiple cytokines with tumor necrosis factor (TNF) being a key player. Few studies, however, have described the effects of anti-TNF therapies on generalized bone loss.
Objective: To study the effects of anti-TNF therapies on the bone mineral density (BMD) of early RA patients and to correlate the BMD measurements with serum receptor activator of NFkB ligand (RANKL) and osteprotegerin (OPG).
Methods: This is a single center study of 40 subjects with active RA (disease activity scores of 3.2 or more) that are naïve to anti-TNF therapy and receiving stable doses of disease-modifying drugs. Patients were treated with adalimumab 40 mg every other week or etanercept (25 mg twice a week or 50 mg once a week). Subjects were allowed to be on a maximum daily dose of 10 mg of prednisone or an equivalent dose. Subjects did not require or were not willing to take medications for osteoporosis. DAS28 assessments were done at baseline, 12 and 24 weeks. Bone mineral density (BMD) measurements of the lumbar spine (LS) and hips were done using a Lunar Prodigy x-ray absorptiometer prior to the first dose of anti-TNF therapy and at week 52. Serum RANKL and OPG levels were measured by ELISA at baseline and at weeks 24 and 52.
Results: The 8 subjects (females, 5; males, 3) who have completed 1 year of anti-TNF therapy had a mean age of 57 years. The mean DAS28 score improved from 4.8 at baseline to 3.5 at 24 weeks. Five patients had a good DAS28 response, 2 had a moderate response, and 1 was a non-responder. The BMD at the LS increased in 5, decreased in 2, and did not change in 1. The mean BMD for the group as a whole did not change with treatment (1.22g/cm2 to 1.21g/cm2) between baseline and week 52. Among the 5 patients with an increase in BMD, 4 had had a good DAS28 response and one had a moderate DAS28 response; whereas, among the 2 patients with a decrease in BMD, 1 was a DAS28 non-responder and 1 had had a good DAS28 response. The patient with no significant change in BMD had a moderate DAS28 response. Serum RANKL levels decreased significantly with treatment from 2381 pg/ml (+/- 3025) at baseline to 921 pg/ml (+/- 1630) at week 52 (p=0.03). Interestingly, at 24 weeks, the serum RANKL was decreased in those with improved BMD (mean RANKL 1994.4 pg/ml at baseline and 1298.2pg/ml at week 24), but was essentially unchanged in those with decreased/ unchanged BMD (mean RANKL 3025.7 pg/ml at baseline and 3029.7 pg/ml at week 24). In the 5 subjects with increased BMD, RANKL levels were decreased in 4 of the subjects and increased in 1 subject. Among the 2 patients with a decrease in BMD, 1 had an increase and 1 had a decrease in RANKL levels. The remaining subject with no change in BMD also had no change in RANKL level. No relationship was noted between BMD at the LS and OPG levels.
Conclusion: Anti-TNF therapy improves BMD at the lumbar spine in a subset of RA patients. The increase in BMD is associated with a decrease in disease activity and may be mediated by a suppression of serum RANKL levels.
A. P. Anandarajah,
Abbott Immunology Pharmaceuticals,
Y. G. Chiu,
J. H. Anolik,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-tnf-therapies-improve-bone-mineral-density-at-the-lumbar-spine-of-ra-patients-by-decreasing-disease-activity-and-suppressing-serum-rankl-levels/