1 Introduction
Rheumatoid arthritis (RA) is a chronic inflammatory disease involving joint pain, joint erosion, and eventually joint destruction [1]. Dyslipidemia is associated with active RA increasing the risk of cardiovascular events, which are the most common cause for mortality. Cardiovascular morbidity is increased more than twofold in RA patients compared to the general population. A wide range of cardiovascular diseases occur in RA patients, including atherosclerosis, thrombosis, and myocardial infarction, heart failure, valvular heart disease, arrhythmia, aortic aneurysms, myo-, peri and endocarditis, vasculitis, rheumatoid cardiac nodules, and cardiac amyloidosis [2-6]. The risk of cardiovascular disease in RA remains high even after adjustment for known cardiovascular risk factors including use of particular medications. Inflammation likely plays a prominent role. Proinflammatory cytokines such as TNF-α, IL-1β, and IL-6, which are found in the synovial tissue, are also found in the circulation [7-9]. These circulating cytokines alter various aspects of metabolism in distant organs, including adipose tissue, skeletal muscle, liver, and vascular endothelium [10, 11]. A spectrum of proatherogenic changes result that include endothelial dysfunction, insulin resistance, and dyslipidemia, prothrombotic effects, and pro-oxidative stress [12-15].
Various studies have been found inconsistent results regarding correlations between inflammation and alterations in particular plasma lipids in the patients with RA who have been given different regimens. A study indicated that HDL-C (high density lipoprotein-cholesterol) were elevated in the patients with RA after treatment of adalimumab for 2 weeks, but LDL-C (low density lipoprotein-cholesterol) and TG (triglycerides) levels were not changed significantly [16]. Another study, in which infliximab was given for 2 years to patients with early RA showed that the levels of TC (total cholesterol), LDL-C and the atherogenic index increased during 24 months, while HDL-C initially increased concomitant with the three lipid parameters, and then decreased significantly after 3 months until the end of the study [17]. The literatures reported that atherogenic index remained constant, while other lipids such as TC, or HDL-C, or LDL-C, or TG increased significantly using infliximab in the patients with active RA for 3 weeks to 6 months [18-20]. In long-term study, the notable findings were that HDL-C, ApoA1 decreased and atherogenic index increased after treatment with DMARDs (disease-modifying anti-rheumatic drugs) and prednisolone in the patients with RA follow-up over 12-year period [21]. Overall, Dyslipidemia is a common complication in rheumatoid arthritis. The lipid profiles varied when disease activity was modified with intervention of drugs. Thereby, dyslipidemia may be attenuated or induced in RA.
Technetium-99 conjugated with methylene diphosphonate (99Tc-MDP, Yunke Pharmaceutical Industry, China), is an anti-inflammatory drug patented in China (patent no. ZL94113006.1). Previous studies demonstrated that 99Tc-MDP inhibits MAPK (mitogen-activated protein kinase) signaling thus reducing the production of proinflammatory cytokines such as IL-1β and IL-6 [22]. Additional studies suggested that 99Tc-MDP reduced joint swelling by regulating the levels of BAP, TRAP and DKK-1[23]. Bone destruction was reduced and the rebuilding new bone enhanced by99Tc-MDP in animal models of arthritis [24]. Thus,99Tc-MDP had not only an effect on against inflammation and also on disease modifying in the patients with active RA. To date, 99Tc-MDP was widely used to treat the patients with active RA in China for its efficacy and inexpensive. Same thing, glucocorticoids are also benefit to active RA, such as reducing disease activity and pain, as well as protective effects on joint destruction [25]. Glucocorticoids are also known, reversible cause of dyslipidemia [26]. 99Tc-MDP combined with oral glucocorticoids were often used to the patients with active RA in China. No studies have evaluated whether 99Tc-MDP and or glucocorticoids improves the dyslipidemia seen in patients with active RA. This study was designed to evaluate this issue.