The present study observed significant differences related to the change of mTSS and ERO between bisphosphonate treatment group and denosumab treatment group in patients with a positive anti-CCP antibody status at 12 and 24 months. In contrast, there was no significant difference in the change of JSN. Similarly, significant differences were observed in the change of BMD of femoral neck and total hip between the groups. However, there was no significant difference in the change of BMD of lumbar spine. These results are consistent with previously conducted large-scale studies [11,18,21]. In this study, patients undergoing bDMARDs treatment were enrolled in both groups. Denosumab treatment was effective for the inhibition of bone erosion, even in the presence of bDMARDs. The present study included the patients with switching treatment from bisphosphonate to denosumab and demonstrated the efficacy of the switching treatment for the inhibition of the bone erosion and destruction, like as the improvement of BMD in patients with RA.
Previous studies have also discussed the efficacy of denosumab for the inhibition of bone erosion. The changes in mTSS were remarkably greater in patients with anti-CCP antibodies . The anti-CCP antibody titer has been demonstrated as a predictor of bone erosion and destruction in patients with RA [28,29]. Patients with anti-CCP antibodies were likely to have the risk of advanced radiographic progression. However, denosumab demonstrated significant inhibition of bone erosion in patients with anti-CCP antibodies . These results were consisted with those of present study. These findings indicted that denosumab is expected to suppress the progression of bone erosion and destruction in patients with anti-CCP antibody positive status.
Previous studies were performed to identify the effect of denosumab treatment on the inhibition of bone erosion and destruction in The patients with RA without treatment history of bisphosphonate and bDMARDs [11,18,21]. Osteoporosis treatment guidelines recommend bisphosphonate at first-line treatment for patient with risks of osteoporosis and osteoporotic fractures [24,25]. Patients with rheumatological disease have the high risks of general bone loss and osteoporotic fractures, and should be treated with bisphosphonate or denosumab [30,31]. Therefore, patients with RA without a history of bisphosphonate and bDMARD treatment seemed to be uncommon and different from actual clinical settings. In contrast, some studies indicated that the effect of switching treatment from bisphosphonates to denosumab for the improvement of BMD in patients with RA. However, previous studies did not demonstrate the effect of the prevention of bone erosion and destruction by switching bisphosphonates to denosumab [32,33]. Since the present study included patients treated with bDMARDs and bisphosphonates, it can be assumed that the study was conducted under conditions similar to actual clinical practice. The present study was the first to demonstrate the efficacy of the switching treatment from bisphosphonate to denosumab for the inhibition of bone erosion and destruction.
The mTSS was the sum of ERO and JSN. The significant difference in mTSS and ERO between the two groups was considered to reflect the inhibitory effect of denosumab on bone erosion. On the other hand, there was no significant difference in JSN, suggesting that neither denosumab nor bisphosphonate had an inhibitory effect on cartilage destruction. In this study, the increase in mTSS at 12 months in the bisphosphonate and denosumab groups exceeded 0.5, which did not correspond to structural remission . However, a higher structural remission rate (the change of mTSS ≤ 0.5) was observed in the denosumab treatment group (28 vs. 58.9%; p<0.001). The results suggest that switching denosumab treatment from bisphosphonate may be advantageous for structural remission.
In this study, we compared and observed the inhibitory effect of denosumab on bone erosion and destruction at 12 and 24 months after switching treatment. Previous studies have confirmed the inhibitory effect of denosumab on bone erosion at 12 months [11,18,21], but its effects over a longer period of time remain undetermined. To our best knowledge, the present study was the first to demonstrate the inhibitory effect of denosumab on inhibition of bone erosion and destruction over a 24-month period.
The results of the present study demonstrated that the changes in BMD of femoral neck and total hip were significantly higher in denosumab group. In contrast, there was no significant difference in the change of BMD of lumbar spine. The participants in this study fulfilled the criteria of either bisphosphonate continuation group or the denosumab switchover group; no bisphosphonate-naive patients were included. Therefore, we considered the possibility that significant differences in BMD of lumbar spine was not observed between the two groups due to the effect of the prior bisphosphonate use. Furthermore, a previous study reported that degenerative disease of the lumbar spine and previous vertebral fracture increased the BMD of the lumbar spine in elderly patients . Other studies have reported that the BMD of the femur had a stronger association with the risk factors of osteoporosis compared to the BMD of the lumbar spine in patients with rheumatological diseases [5,35]. The authors considered that lack of a significant difference in the change of lumbar spine BMD may have been due to its susceptibility to age-related degeneration and vertebral fractures.
There are several limitations in the present study. First, the present study was performed as a retrospective study and the number of patients was small. Authors did not perform the adjustment of confounding factors of participants in this study. Further large-scale prospective studies with the adjustment of confounding factors are required to confirm the results in this study. Second, the treatment agents of rheumatoid arthritis and treatment duration were not uniform among the study patients. Therefore, future studies should consider assessing the treatment effect of denosumab for erosion inhibition in patients with uniform RA treatment history. Third, the types of bisphosphonates used prior to the enrollment of this study and the duration of their use were not uniform. The types of bisphosphonates used continuously were also not uniform. Fourth, the measurement of anti-CCP antibody was not performed after denosumab treatment. The effect of denosumab for decreasing the titer of anti-CCP antibody remained unclear. Finally, the serum bone turnover markers and serum vitamin D levels were not measured in the present study.
In conclusion, the present study indicated significant differences related to the change of mTSS and ERO between bisphosphonate and denosumab treatment groups in the patients with a positive anti-CCP antibody status. In contrast, denosumab treatment did not affect the change of JSN. Similarly, denosumab treatment provided greater improvement in the BMD of the femoral neck and total hip. Denosumab treatment was effective for the inhibition of bone erosion, even in the presence of bDMARDs. Denosumab may contribute to both the treatment of osteoporosis and the prevention of the destructive arthritis in patients with RA. The results of present study are exploratory, and the authors consider that further follow-up is needed for causal inference.