A total of 35 patients with RA were included in this study. Of these patients, 18 were on conventional synthetic DMARDs, 12 were receiving biologic DMARDs, and 5 were taking target-specific DMARDs. Table 1 summarizes the general demographic and clinical characteristics of the participants.
Table 1
Demographic and clinical characteristics of the participants
|
N
|
Mean/standard deviation
|
Age (years)
|
35
|
47.2 (± 9.05)
|
BMI (kg/m²)
|
35
|
27.5 (± 6.27)
|
Female
|
30 (85.7%)
|
-
|
Disease duration (years)
|
35
|
8.4 (± 6.67)
|
DAS28-ESR
|
35
|
3.1 (± 1.42)
|
DAS28-CRP
|
35
|
2.6 (± 1.30)
|
CTX (ng/mL)
|
35
|
0.424 (± 0.231)
|
LS BMD
|
35
|
1.095 (± 0.181)
|
FN BMD
|
34
|
0.907 (± 0.159)
|
TF BMD
|
33
|
0.911 (± 0.143)
|
Prednisone dose (mg/day)
|
35
|
5.643 (± 5.366)
|
CRP (mg/dL)
|
35
|
0.95 (± 1.1)
|
|
Count
|
Cumulative sum
|
DMARD class
|
|
|
csDMARD
|
18
|
18
|
tsDMARD
|
5
|
23
|
bDMARD
|
12
|
35
|
BMI body mass index, DAS28 Disease Activity Score in 28 Joints, ESR erythrocyte sedimentation rate, CRP C-reactive protein, CTX C-terminal telopeptide, LS BMD lumbar spine bone mineral density, FN BMD femoral neck BMD, TF BMD total femur BMD, DMARD disease-modifying antirheumatic drug, csDMARD conventional synthetic DMARD, tsDMARD target-specific DMARD, bDMARD biologic DMARD
Overall, 77.1% of patients were seropositive for RA, predominantly with high rheumatoid factor titers (45.7%). Serum CRP levels were within the normal range (< 0.5 mg/dL) in 65.7% of patients, whereas the remaining 34.3% of patients had serum CRP levels ranging from 0.6 to 5.0 mg/dL. Disease activity was assessed by calculating DAS28-CRP, which indicated that nearly 66% of patients achieved the RA therapeutic target (i.e., remission or low disease activity), 25.7% had moderate disease activity, and 8.6% exhibited high disease activity.
The analysis of corticosteroids showed that 37.2% of patients continuously used a prednisone dose of > 5 mg/day. In the evaluation of background therapy for RA, 80% of participants were on methotrexate, which was administered either as monotherapy or in combination with other biologic and/or target-specific DMARDs. Additionally, 5 patients (14.3%) were taking leflunomide. Of all patients, 34.3% (n = 12) were on biologic DMARDs. The sample also included 5 patients using Janus kinase inhibitors (3 patients on tofacitinib and 2 patients on baricitinib).
Bone health was assessed using additional risk factors for low bone mass. The results indicated that 75% (n = 24) of patients were consuming a calcium-poor diet (daily intake of < 800 mg/day). Without entering the BMD data, we used the FRAX/NOGG tool for 32 patients, all of whom being older than 40 years. Of these patients, 63% were in the yellow zone, with formal indication for bone densitometry; 23% were already in the red zone, with formal indication for osteoporosis treatment; and only 5.7% (n = 2) were in the green zone.
As shown in Fig. 1, the comparison of CTX levels between different treatment groups revealed no significant difference (p = 0.603).
No significant between-group differences were found when assessing BMD by densitometry at three usual sites (Table 2).
Table 2
Comparison of BMD values between the treatment groups
|
Mean
Lumbar spine BMD
|
Standard deviation
|
Minimum
-95.00%
|
Maximum
+95.00%
|
csDMARD
|
1.095
|
0.042
|
1.007
|
1.184
|
tsDMARD
|
1.197
|
0.091
|
0.944
|
1.451
|
bDMARD
|
1.051
|
0.050
|
0.940
|
1.162
|
|
Femoral neck BMD
|
|
|
|
csDMARD
|
0.933
|
0.047
|
0.835
|
1.032
|
tsDMARD
|
0.867
|
0.064
|
0.688
|
1.046
|
bDMARD
|
0.887
|
0.032
|
0.816
|
0.958
|
|
Total femur BMD
|
|
|
|
csDMARD
|
0.917
|
0.041
|
0.829
|
1.005
|
tsDMARD
|
0.898
|
0.070
|
0.703
|
1.093
|
bDMARD
|
0.909
|
0.034
|
0.835
|
0.983
|
BMD bone mineral density, DMARD disease-modifying antirheumatic drug, csDMARD conventional synthetic DMARD, tsDMARD target-specific DMARD, bDMARD biologic DMARD
The two main pro-inflammatory cytokines in RA—namely, TNF-α and IL-6—were analyzed in this study, as shown in Fig. 2. TNF-α was detected in all participants, at an average level of 92.67 pg/mL (standard deviation: ±32.62); this cytokine was found even in healthy controls, at an average level of 99.43 pg/mL (standard deviation: ±36.93).
IL-6 was detected in some patients, at an average level of 34.07 pg/mL (range: 0.0–931.56 pg/mL) in the RA group and 3.12 pg/mL (standard deviation: ±7.44) in healthy controls. In the RA group, patients on biologic DMARDs had the highest mean IL-6 level at 92.98 pg/mL, whereas those on conventional synthetic DMARDs had a mean level of 4.26 pg/mL. Analysis of IL-6 levels did not show any significant difference between the groups (p = 0.286).
We calculated the Pearson product-moment correlation coefficient (Table 3) to assess the correlation with the study variables, particularly in the biologic DMARD group. The cytokine level did not show a correlation with any other study variable; however, the prednisone dose was positively correlated with DAS28-CRP.
Table 3
Correlation between the variables of interest in the biologic DMARD group
|
|
|
|
|
|
|
|
|
|
CTX
|
1.00
|
-0.34
|
-0.43
|
-0.46
|
-0.23
|
0.18
|
0.33
|
0.18
|
0.47
|
|
-0.34
|
1.00
|
0.89
|
0.87
|
0.04
|
-0.41
|
-0.29
|
0.01
|
0.04
|
|
-0.43
|
0.89
|
1.00
|
0.93
|
0.04
|
-0.29
|
-0.49
|
-0.22
|
0.00
|
|
-0.46
|
0.87
|
0.93
|
1.00
|
0.12
|
-0.29
|
-0.24
|
0.04
|
0.15
|
|
-0.23
|
0.03
|
0.04
|
0.12
|
1.00
|
-0.21
|
0.01
|
-0.00
|
-0.32
|
|
0.18
|
-0.41
|
-0.29
|
-0.29
|
-0.21
|
1.00
|
-0.12
|
-0.18
|
0.02
|
|
0.33
|
-0.29
|
-0.49
|
-0.24
|
0.01
|
-0.12
|
1.00
|
0.89
|
0.61
|
|
0.18
|
0.01
|
-0.22
|
0.04
|
-0.00
|
-0.18
|
0.89
|
1.00
|
0.54
|
|
0.47
|
0.04
|
0.01
|
0.15
|
-0.31
|
0.02
|
0.61
|
0.54
|
1.00
|
The values presented above are the Pearson product-moment correlation coefficient (r), whereas the values marked in bold indicated p < 0.01
bDMARD biologic disease-modifying antirheumatic drug, CTX C-terminal telopeptide, LS BMD lumbar spine bone mineral density, FN BMD femoral neck bone mineral density, TF BMD total femur bone mineral density, TNF-α tumor necrosis factor-α, IL-6 interleukin-6, DAS28 Disease Activity Score in 28 Joints, ESR erythrocyte sedimentation rate, CRP C-reactive protein