4 Discussions
99Tc-MDP, one of common anti-inflammation drug in China, which is widely used to active RA because of its efficacy and low price. Glucocorticoids are the common agents including prednisone, methylprednisone, and betamethasone, beclomethasone dipropionate, prednisolone, hydrocortisone, dexamethasone and so on, which are being widely used to different diseases for its anti-inflammation and immunosuppressive function [28, 29]. Especially, glucocorticoids are often the first-aid drug in emergency or critical situations. In this study, single 99Tc-MDP or combined with oral glucocorticoids are effective to anti-inflammation treatment in the two groups, tender joint counts and swollen joint counts were reduced, sequentially disease activities got down. The inflammatory markers (ESR & CRP) and disease activities were decreased more in the group of99Tc & GC than in the group of99Tc. The results also indicated that combination regimen was superior to single medication when disease activities got worse. So that depending upon the different disease activities, customized therapeutical regimens could be provided for the individual patients.
We found that the inflammatory markers (ESR, CRP) and DAS28 were not only decreased significantly in the patients with RA after a therapeutic course of 99Tc-MDP and or oral glucocorticoids, but the partial lipids were also changed significantly. Therefore, nonfasting lipids including the atherogenic index and ApoB/ApoA1 ratio were reduced significantly. Reduced HDL-C and ApoA1 represent an important factor in the etiology of dyslipidemia in RA [30]. In present study, the level of ApoA1 was increased after treatment of99Tc-MDP and or oral glucocorticoids in both groups. The levels of TC and HDL-C were elevated after treatment in99Tc & GC. The increase of TC might cause by the increased level of HDL-C. Consequently, atherogenic index was decreased. Atherogenic index is regarded as a useful predictor of atherosclerosis by some practitioners [31, 32]. It predicts that the risk of cardiovascular events gets down when atherogenic index is reduced. A largest case-control study from 52 countries investigated which were the strongest risk factors for MI (myocardial infarction) among the ratio of ApoB/ApoA1, smoking, diabetes, hypertension, abdominal obesity, psychosocial, fruits and vegetables, exercise, and alcohol. This study found that all risk factors were statistically related to MI risk. The strongest and also the most prevalent risk factor, was the ratio of ApoB/ApoA1 both in men and women [33, 34]. In a subsequent paper, it also showed that the ratio of ApoB/ApoA1 had the strongest relation to MI-risk compared to all other measured lipids [35]. Although the ratio of ApoB/ApoA1 was decreased significantly after treatment with99Tc-MDP and or glucocorticoids, ApoB/ApoA1has been seen the only significant correlation with ESR in the group of99Tc & GC using line regression analysis, nonsenses of with CRP and DAS28CRP/ESR in the two groups. However, using non parameter Spearman correlation analysis, the ratio of ApoB/ApoA1 was related to CRP, ESR and DAS28CRP/ESR in the group of 99Tc & GC. The possible reason is small size of samples, methodological difference might be a co-factor.
Notably, the levels of TG were increased after the treatment with99Tc-MDP and or oral glucocorticoids. It has been reported that the levels of TG were elevated with oral glucocorticoids in the patients with RA [26, 36-38]. Whether this would influence cardiovascular risk is unclear. The interplay of between lipid profile and inflammation is complicated. The final cardiovascular risk and deleterious outcome depend upon multifactor and variable diseases. Further long-term studies with larger numbers of the patients are needed to address this issue. Furthermore, there are 6 out of 8 lipids changed significantly in the group of 99Tc & GC, while only 3 lipids in the group of 99Tc.The results of two groups showed that the lipids had been changed more using the regimen of99Tc combined with oral glucocorticoids than using 99Tc-MDP alone.
The partial lipids were changed when the inflammation is attenuated using 99Tc-MDP and or Oral glucocorticoids in our observation. There is an intriguing phenomenon that reduced DAS28CRP or ESR was related with the increased CHO, LDL-C and ApoB in the group of 99Tc, whereas reduced CRP, ESR and DAS28CRP/ESR were related with increased ApoA1, HDL-C, and reduced atherogenic index in the group of99Tc & GC. These results indicated that lipid profiles possibly got worse by increased CHO, LDL-C and ApoB though disease activity was decreased in the group of 99Tc. Vice versa, dyslipidemia might be improved by increased ApoA1, HDL-C and reduced atherogenic index when the inflammatory condition got well in the group of 99Tc & GC. The results of two groups presented different correlations of between inflammation and the partial lipids. It indicated that the risk of dyslipidemia should be considered when 99Tc-MDP was used alone. While, Combination therapy of 99Tc-MDP and glucocorticoids would be better for its effects of anti-inflammation and lipid metabolism regulation. Glucocorticoids have a differential effect on lipid profiles in the patients with underlying various diseases. Observational studies showed that the patients treated glucocorticoids exhibited variable changes of HDL-C in asthma, cardiac or renal transplants, and rheumatoid arthritis [39, 40]. The reasons behind the observed difference are factorial. The variable results in HDL-C levels among patients are dose-related and disease dependent [41, 42]. Moreover, glucocorticoid administration may have different short-term and long-term effects on lipids. The previous studies have suggested glucocorticoid-induced hepatic insulin resistance leads to increased production of VLDL and subsequent increased TG levels [43]. The mechanisms through which glucocorticoids and or99Tc-MDP induce dyslipidemia are not yet well elucidated so far.
In conclusion, despite treatment of 99Tc-MDP and or oral glucocorticoids have the limited effects on lipid profiles upon short-term observation and small size of samples, the risk of dyslipidemia should be weighed when administration of99Tc-MDP alone is formulated for the patients with active RA. Combined with oral glucocorticoids may be a good therapeutic regimen but the increasing level of TG should be monitored. Prolonged duration of 99Tc-MDP and or oral glucocorticoid treatment and larger scale of patients will be desired to further address this issue.