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.