| Objective: Rheumatoid arthritis (RA) is a kind of common autoimmune disease. Besides the joints and system involvement, bone mass loss, low bone mineral density (BMD) or even osteoporosis (OP) and fracture can appear in RA. The mechanisms of RA complicated with OP and bone metabolism condition in RA are not entirely clear. Low-dose glucocorticoid (GC) is frequently used in the treatment of RA. While GC itself can cause complications such as OP, its influence on BMD and bone metabolism is still in dispute. This study was designed to investigate: 1 the relationship between RA and OP by means of measurement on BMD through dual-energy X-ray absorptiometry (DXA); 2 the bone metabolism condition of RA by determination of the levels of serum osteoprotegerin (OPG), interleukin-1β(IL-1β) and bone gla protein (BGP) through avidin biotin peroxidase complex enzyme-linked immuno- sorbent assay (ABC-ELISA); 3 the influence of low-dose GC on BMD and bone metabolism through comparing the changes of BMD and indicators related to bone metabolism pre and post low-dose GC treatment; 4 to preliminarily seek for the position of GC in the therapeutic scheme for RA, providing evidence for the application of GC.Methods: Sixty RA inpatients were divided into two groups according to their disease condition: low-dose GC treatment group (group A, 40 patients) and non-GC treatment group (group B, 20 patients). All the patients included were in accord with the American College of Rheumatology (ACR) 1987 revised classification criteria of rheumatoid arthritis, who were not ever continuously treated with GC or disease modifying antirheumatic drugs (DMARD). Twenty healthy subjects were included as control. BMD of RA patients was measured through DXA and the levels of serum OPG, IL-1βand BGP were determined by ABC-ELISA. The clinical data of RA patients were collected such as age, disease duration, blood pressure, fasting blood glucose, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), levels of serum calcium (Ca), phosphorus (P) and alkaline phosphatase (ALKP). All the RA patients were treated with one or two kinds of DMARDs. Besides, those who were complicated with OP were treated with calcium agent. Reexamination was performed 6 months later for BMD, the indicators related to bone metabolism and the clinical data. These data were compared by self-control method.All the data were analyzed by SPSS16.0 for Windows statistical software. The mean number±standard deviation ( x±s) was used to express the measurement data. The t or t'test was adopted for comparison between groups, paired t test for data of pre and post treatment. Chi-square test was used for the comparison of the enumeration data. Linear correlation analysis was performed for correlationship. P value<0.05 was considered significant.Results: 1 The incidence of normal bone mass, low BMD and OP were 18.33%, 25% and 56.67% respectively in 60 RA patients. The incidence of OP was 31.25% in 16 male patients, 65.91% in 44 female patients, 12.5% in 8 premenopausal patients and 77.78% in 36 postmenopausal patients. The incidence of OP in female RA patients was higher than that in the male (χ~2=5.740, P=0.017) and so was in the postmenopausal than in the premenopausal (χ~2=9.678, P=0.002).2 The incidence of OP in lumbar, femoral neck and greater trochanter were 18.33%, 23.33% and 53.33% respectively. There were significant measurement sites differences (χ~2=19.872, P=0.000). The highest incidence of OP was in greater trochanter (53.33%).3 The levels of serum OPG, IL-1βand BGP in RA patients were (71.08±33.47)ng/L, (17.28±8.25)ng/L, (9.73±3.90)μg/L respectively, and (106.19±41.08)ng/L, (7.91±4.36)ng/L, (4.83±2.02)μg/L respectively in the healthy control. Compared with the healthy control, the level of serum OPG in RA patients was significantly lower, while the levels of IL-1βand BGP were significantly higher (P<0.01).4 There was no linear correlation in OPG, IL-1βor BGP (P>0.05). Except the positive correlation between IL-1βand ESR (r=0.271, P=0.036), no linear correlation was obtained between the indicators related to bone metabolism and RF, ESR, CRP (P>0.05).5 RA patients were divided into two groups: OP group (34 patients) and non-OP group (26 patients) according to the complication with OP or not for further comparison. It showed statistical difference in age (P=0.007) and the levels of serum Ca (P=0.007), ALKP (P=0.042), OPG (P=0.040) and IL-1β(P=0.035) between the two groups. The patients in OP group had older ages, lower level of serum Ca but higher levels of serum ALKP, OPG and IL-1βcompared with non-OP group. No statistical significance was obtained in disease duration, the levels of RF, ESR, CRP, Ca, P or ALKP (P>0.05). Compared with the healthy control,both OP and non-OP group had lower levels of serum OPG but higher levels of serum IL-1βand BGP (P<0.05).6 It showed lower BMD in different measurement sites in both low-dose GC and non-GC treatment group after treatment for 6 months but no statistical significance (P>0.05).7 Six months later, in both low-dose GC and non-GC treatment group the levels of RF, ESR, CRP and IL-1βwere decreased significantly (P<0.05) while the level of OPG was increased significantly (P<0.05) as compared with the pretreatment. No statistical significance was obtained in the changes of blood pressure, fasting blood glucose, levels of serum Ca, P or ALKP (P>0.05). The level of BGP in low-dose GC treatment group was decreased significantly (P<0.05) while this change in non-GC treatment group was no statistical significance (P=0.068).8 Except that the descent range of serum IL-1βlevel was significantly higher in low-dose GC treatment group (P=0.016), no statistical significance was obtained in the range of changes in RF, ESR, CRP, OPG or BGP levels pre and post treatment between low-dose GC and non-GC treatment group (P>0.05).9 During the study period, no severe GC-associated complications were observed in low-dose GC treatment group such as fracture, diabetes, severe infection or thrombosis.Conclusions: 1 RA patients have different degree of bone loss and most of them are complicated with low BMD or OP, which is more obvious in the elderly and women. Menopause makes this even worse for female RA patients.2 The degree of bone loss is varying in different measurement sites. For a better overall evaluating the BMD, it is necessary to measure BMD in multiple sites and make a comprehensive analysis.3 Although most of RA patients'clinical data become stable after regular treatment such as DMARD and GC for 6 months, the trend that BMD decreases gradually still exists. Emphasis should be put on regular monitoring of BMD for RA patients.4 Bone turnover rate is increased and bone formation is parallel with bone resorption in RA patients, which is more obvious in those who are complicated with OP. With the improvement of disease condition, bone turnover rate is decreased.5 Short-term treatment combined with low-dose GC has no significant negative influence on BMD and can decrease bone turnover rate better in RA patients. Short-term and low-dose GC treatment is safe and effective. |
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