Background/Purpose: Previous studies suggest that antibodies to citrullinated protein antigens (ACPA) contribute to decreased hand bone mineral density (BMD) in RA-free individuals. No evidence exists with regard to associations of ACPA or rheumatoid factor (RF) with general osteoporosis or more clinically relevant lumbar spine BMD; a common site for compression fractures, immobility, and pain. Therefore, we sought to determine whether RA-related autoantibodies were associated with lumbar BMD in a community based population sample in order to help delineate whether previous findings of decreased hand BMD in those with RA-related autoantibodies may also indicate systemic bone changes.

Methods: In the Multi-Ethnic Study of Atherosclerosis (MESA), a multi-ethnic, multi-center, prospective study of community-dwelling individuals designed to study characteristics of subclinical and clinical cardiovascular disease, we evaluated 1924 participants with measures of RA-related autoantibodies: RF IgA and IgM isotypes and anti-cyclic citrullinated peptide (anti-CCP) antibodies, as well as volumetric BMD (vBMD) from the third lumbar vertebra (L3) by computed tomography. RA-related autoantibodies were analyzed as dichotomous variables (positive vs negative) based on pre-specified cut-offs, and vBMD was analyzed as a continuous variable. We investigated associations between RA-related autoantibody positivity and vBMD using ANCOVA, stratified by sex a priori, and adjusting for age, race, weight, diabetes, self-reported arthritis, current smoking, c-reactive protein, education, estimated glomerular filtration rate, albumin/creatinine ratio, physical activity (mets/week), hypertension, alcohol use, thiazide and loop diuretics (and hormone replacement therapy in women).

Results: Among 1924 MESA participants (956 women), the mean age was 62 years, and 40% were Caucasian, 13% were Chinese, 20% were African American, and 26% were Hispanic. Mean L3 vBMD was 111 mg/cc in women and 121 mg/cc in men. Twenty percent were positive for RF, and 1% of men and 2% of women were positive for anti-CCP (Table 1). In women, there was no association of vBMD with RF positivity or anti-CCP positivity in either minimally or fully adjusted models.  Results were similar in men. Sensitivity analysis stratified by self-reported arthritis showed similar results.

Conclusion: In a multi-ethnic community-based population sample, RA-related autoantibody positivity was not significantly associated with lumbar BMD. As this finding was in contrast to previous findings in hand BMD, further research is needed to determine whether bone changes are local (e.g., RA-specific joints) or systemic.