Data suggest that patients with rheumatoid arthritis (RA) are at an increased risk of osteoporosis and fractures when compared with the general population. Recent studies have found that patients diagnosed with RA have greater loss of bone mass than expected in early disease. “Treatment for both RA and osteoporosis have continuously improved during the past few decades,” explains Lisa Theander, PhD-candidate. “In light of these improvements, re-evaluation of the changes in bone mineral density (BMD) experienced by patients following RA diagnosis is needed.” To do so, Theander and colleagues sought to examine the progression of BMD in patients with RA during the first 10 years after diagnosis.

BMD Research

For a study published in RMD Open, the researchers followed more than 200 patients with RA to investigate whether they had lower-than-average BMD at diagnosis, whether BMD changed during the first 10 years, and if baseline factors predicted bone mass changes. Participants had been experiencing symptoms for less than 12 months at time of enrollment. Treatment followed standardized care for RA without any specified protocol for antirheumatic treatment, before the treat-to-target protocol was standard.

All patients were examined upon enrollment and then at 6, 12, 24, 60, and 120 months by the same rheumatologist. Additionally, each had their left femoral neck and L2-L4 vertebrae measured with dual-energy x-ray absorptiometry (DXA) upon enrollment and follow-up at 2, 5, and 10 years. “The mean z-scores over the study period were estimated using mixed linear effect models, where the intercept corresponded to the estimated mean z-score at baseline, based on the regression line,” explains Theander. “The impact of baseline characteristics on the mean z-score over 10 years was also analyzed in mixed linear effect models, in univariate and, if significant in univariate models, in multivariate models.” Smoking and postmenopausal status, in women, were also included in multivariate models. The study team analyzed BMD changes using the paired T-test during 0-2 years, 2-5 years, 5-10 years, 0-5 years, and 0-10 years. Femoral neck and L2-L4 measurements were analyzed separately and stratified by sex.

Accessing Data

BMD z-scores were numerically lower in men than in women at enrollment and remained lower throughout the study. Femoral neck BMD was reduced at diagnosis in male patients and had decreased significantly but marginally after 5 years of follow up (mean change in Z-score -0.23, -0.43 to -0.03). “Early intervention with antiosteoporotic treatment in men could be beneficial and needs to be further studied,” suggests Theander. In contrast, women with early RA had a greater chance of retaining their BMD.

The study team found that higher BMI was the only baseline factor that predicted high z-scores over time in both femoral neck and L2-L4, in men and women. Postmenopausal status proved to be an indicator for reduced femoral neck BMD (Table). No disease-related factors had a significant impact on BMD in men, while anti-CCP antibodies in women were associated with lower z-scores in the L2-L4. “There have been inconsistent reports of associations between change in BMD and RA severity,” emphasizes Theander. “This may be due to difficulties in obtaining a robust marker for cumulative disease activity and severity over time. Ongoing treatment with both antirheumatic and antiosteoporotic drugs and changes in therapy and disease course over time may limit long-term prediction of BMD in this study.”

Looking Forward

Theander believes that because BMD is lower in men at time of RA diagnosis, research should be dedicated to early intervention against bone loss in men with RA. “There are also ongoing discussions on the topic of the potential positive effects of glucocorticosteroids on BMD due to their anti-inflammatory effects in RA,” adds Theander, “and it would be interesting to relate results of DXA measurements to the actual risk of fractures in patients with RA specifically.”