In this study, the prevalence of patients with cervical lesions was 57%. RA disease duration, use of prednisolone, biological agents, and BMD of the femoral neck were identified as risk factors of cervical lesions.
The cervical spine is frequently involved in patients with RA, and neural impairment is a consequent complication. Irreversible spinal cord damage, difficulty with ambulation, respiratory dysfunction, and even sudden death can occur . Once neurological deficits occur, neural impairment becomes progressive , and even surgical treatment cannot prevent neurological deterioration . Therefore, RA cervical lesions are still a major health concern. Several studies have reported the risk factors of cervical lesions in RA patients [6-8]. However, it has not been well investigated after the use of biological agents became more popular.
The registration of biological agents has changed the standard of care for patients with rheumatoid arthritis. The available biological agents are anti-proinflammatory cytokine therapies, such as TNFα blockers and a T cell activation inhibitor .
Terashima et al. reported that mutilating changes at baseline, corticosteroid administration, and previous joint surgery were predictors of severe aggravation of cervical spine instabilities in RA . Kaito et al. also reported that disease duration and Steinbrocker stage were identified as independent risk factors for the incidence of cervical lesions . In this study, the multivariate analysis showed that RA disease duration, use of prednisolone, use of biological agents, and BMD of the femoral neck were risk factors of cervical lesions. Although biological agents can prevent the onset of cervical lesions, pre-existing cervical lesions cannot be reversed .
Several studies have shown that the prevalence of cervical lesions in RA patients ranged from 32% to 57% [4-8]. Fujiwara et al. prospectively examined 173 patients to clarify the development and progression of cervical spinal involvement in RA. The incidence of cervical lesions was 43% at 12.3 years of RA and 57% at 16.5 years of RA. As follow-up proceeded, more cases of cervical lesions have become apparent, indicating that cervical lesions are progressive . In Japan, biological agents were approved in 2003. This might have had an influence on stabilizing RA cervical lesions. In fact, Takahashi et al. reported that 42% of 220 patients from 2010 to 2011 had cervical spine instability. The prevalence has decreased since the approval of biological agents. However, there were no effects of MTX and biological agents on cervical instability . Kaito et al. reported that the incidence of patients with RA onset after 2000 with any cervical lesions was 31.8%. Biological agents effectively prevented the emergence of new cervical lesions but could not prevent the progression of pre-existing cervical lesions [5, 9].
Our study indicated that the prevalence of patients with cervical lesions was 57%. There were 78 patients with AAS, 42 with SAS, and 31 with VS. This prevalence is higher than that in recent studies in this era of biological agents [4, 5]. This might be due to the mean RA disease duration in our study, which was 14.3 years compared to the 8.5 and 11.1 years
reported in previous studies. In addition, a large proportion of patients with more advanced diseases might be treated by the use of biological agents.
There have been few reports that described the association between RA cervical lesions and osteoporosis. Neva et al. reported that the severity of atlantoaxial disorders positively correlated with the grade of destruction in evaluated joints. Furthermore, patients with atlantoaxial disorders presented with decreased BMD of the femoral neck . VS usually occurs after AAS. VS is considered to be a serious condition in patients with RA because it can be associated with a poor survival rate and sudden death . Dokai et al. hypothesized that osteoporosis could affect the progression of VS. Their results indicated that VS could be induced by the collapse of the lateral masses in the upper cervical spine. The risk factors for VS development were age, RA symptom duration, and BMD (lumbar). However, they could not show a statistically significant relationship between osteoporosis and VS development . In our current study, the prevalence of BMD of the femoral neck was 58.4% in the VS group, which was significantly lower than the 65.9% observed in the non-VS group. However, the difference in BMD of the lumbar spine did not show any statistical significance. This discrepancy might be due to osteophytes and endplate erosions that have been described to affect the measurement of BMD at the lumbar spine [10, 18]. Nevertheless, our results indicated that the general status of osteoporosis could contribute to the development of VS. The appropriate treatment of BMD deficiency may prevent the development of VS. Tanaka et al. reported that denosumab could prevent the progression of bone erosion in the early stage of RA and play a useful role in anti-osteoporotic therapy. However, denosumab has no effect on joint inflammation or cartilage destruction in RA . The complex osteoimmunological network in patients with RA suggests that the powerful anti-inflammatory activity of biological agents beyond the control of the disease was likely to reduce osteoporosis and fracture risk . Therefore, a combination of biological agents and denosumab may be effective for the prevention of VS. Further studies are required to establish these treatments.
There are several limitations to this study. First, in this cross-sectional study, we reviewed patients with varying degrees of spinal instability, and we did not consider the duration of RA treatment and the dosage of medications. This may have led to a selection bias, which may have resulted in the use of biological agents being identified as a risk factor of RA cervical lesions. Second, we did not access the data on clinical and neurological symptoms. Only patients with RA who complained of symptoms of cervical lesions were included in this study. It is possible that only more frail patients had a bone scan as opposed to all patients with RA to limit selection bias towards patients with lower BMD. Third, this was a cross-sectional study; consequently, disease activity was only reflected over a certain period of time. A longitudinal evaluation was not performed.