Bisphosphonates Effect On Bone Metabolism And Bone Mineral Density In Female Patients With Rheumatoid Arthritis

Objective: Rheumatoid arthritis (RA) is a kind of inflammatory autoim- mune diseases, which can encroach bones, joints and systems, lead to bones and joints destruction, bone mass and bone strength loss, osteopenia or even osteoporosis (OP). However, the mechanism of OP complicated with RA was unresolved, the changes of bone metabolism in RA patients were still controversial, and there was no specific standardization criterion for the treatment of OP complicated with RA. Bisphosphonates (BPs) were used for the treatment of RA. The objective of this study was to investigate the relationship between RA and bone metabolism condition, the role of BPs in treatment through determining bone mineral density (BMD), the levels of parameter of bone metabolism and clinical index before and after treatment, and provide new evidence for the treatment of RA patients.Methods: 36 healthy people were selected as control group. While 44 RA patients were envolved in this study. The diagnosis of RA patients was consistent with the major classification criteria revised by American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR). 44 RA patients were allocated into two groups: BPs and non-BPs treatment group. All the patients took one kind of NSAIDs and one or two kinds of disease modifying antirheumatic drugs (DMARD), and glucocor- ticoid or biologic agent were never continuously used. Serum levels of bone alkalin phosphatase (BALP), soluble fibroblast growth factor-23 (FGF-23), tartrate-resistant acid phosphatase 5b (TRACP-5b) and interleukin -23(IL-23) were assessment by avidin biotin peroxidase complex enzyme-linked imm- unosorbent assay (ABC-ELISA). The BMD were measured with dual-energy X-ray absorptiometry (DEXA). The clinical data associated were collected such as disease duration, age, erythrocyte sedimentation rate (ESR), rheuma- toid factor (RF), C-reactive protein (CRP), alkaline phosphatase (AKLP). These data of RA group were collected at baseline and at 9 months endpoint.Statistical analyses were performed with SPSS 13.0 software for Windows. All the measurement data which met normal distribution were expressed as mean number±standard deviation ( x±s). The t or t'test was adopted for comparison between groups, and paired t test was adopted for data of pre and post treatment.The measurement data which did not meet normal distribution was expressed by median and quartile range (M, QR), and rank-sum test was adopted. Chi-square test was used to compare the ranked data. Linear correlation analysis was used for correlationship. P or Z values<0.05 were considered significant.Results: 1 The demographic details: All the subjects were female. In nor- mal controls, the mean age was (57.03±10.61) years. In RA group the mean age of was (53.58±7.25) years, and average disease duration of (62.45±10.48) months. In the group of 22 patients with BPs treatment, the mean age was (57.93±8.67) years, and average disease duration of (68.33±11.65) months. In the group of 22 patients with non-BPs treatment, the mean age was (50.78±8.13) years, and average disease duration of (59.31±12.49) months. There were no differences between control group and RA group in age and gender(P>0.05), and also no significant differences between BPs group and non-BPs group in the traditional parameters of disease activity, such as ESR, CRP and RF(P>0.05).2 Results of bone density of RA group before treatment: The incidence of OP, osteopenia and normal BMD were 63.64%, 22.73% and 13.64% respectively. Among lumbar, greater trochanter and femoral neck, the incidence of OP had statistic significant differences (18.33%, 23.33% and 53.33% respectively), and the highest site was greater trochanter (50.00%). No statistical difference between BPs group and non-BPs group(P>0.05).3 Serum levels of bone metabolic indexes before treatment: Compared with normal controls, the serum level in RA group of TRACP-5b, BALP and IL-23 were significantly higher(P<0.05), and the level of FGF-23 was lower,but statistically significant (t=-1.361, P=0.088). There were no statistically different in bone metabolic indexes between BPs group and non-BPs group (P>0.05).4 The change of BMD before and after treatment:In BPs group,the BMD of lumbar and greater trochenter increased significantly after treatment of 9 months(P<0.05).There was no significantly change in non-BPs group except that BMD of greater trochanter was lower than pretreatment(P>0.05).5 The changes of the serum levels of bone metabolic indexes in RA group before and after treatment: Compared with pretreatment, the serum levels of IL-23, TRACP-5b and FGF-23 decreased, the level of BALP increased, and the different was significantly except TRACP-5b. Those changes in BPs group were significantly, while no statistical significance was obtained in non-BPs group. The range of changes in bone metabolic levels were significant different between BPs group and non-BPs group except FGF-23.6 The changes of clinical indexes in RA group before and after treatment: The levels of RF, ESR, CRP, PLT, IgG, IgM, IgA, C3, C4, morning stiffness duration and DAS28 were significant decreased after treatment. And the descent ranges of DAS28 and morning stiffness duration of were significant higher in BPs group.7 Correlation between bone metabolic indexe and clinical data: According to linear correlation analysis, there were positive correlation between TRACP-5b with IL-23 and RF. The level of BALP was positively correlated with AKLP while negatively correlated with FGF-23. The levels of ESR, disease duration and DAS28 were negatively correlated with the levels of FGF-23. The BMD of greater trochanter was positively correlated with BMI while negatively correlated with the levels of BALP.There were no significant linear correlation among other data.8 During treatment period, there were no adverse reactions such as phlebitis, rash, fever, mucosa ulcer, intestinal symptoms and drug-induced liver injury, etc. Conclusions: 1 Female RA patients had tendence of OP or osteopenia. The loss of bone mass could appear in every stage of RA, and it was different in diverse measurement sites.2 There was abnormality in bone metabolism of RA.The bone conversion of RA was high, both bone formation and bone resorption were strengthened at the same time, and the degree of bone resorption strengthened more than bone formation.3 Only seldom statistical correlations existed among bone metabolism indexes, BMD, and clinic datas. It suggested that multi-factors and long-term effectiveness led to the secondary OP of RA.4 BPs could enhance bone mass, decrease bone conversion. BPs were major restraint of bone resorption and might be promotion of bone formation.5 DMARDs treatment combined with BPs could decrease the levels of inflammatory index and effectively treat RA patients.