Low serum albumin concentration is associated with increased risk of osteoporosis in postmenopausal patients with rheumatoid arthritis

BackgroundThe risk of osteoporosis in patients with rheumatoid arthritis (RA) is frequently overlooked, and investigating a simple indicator in routine care may be beneficial to motivate osteoporosis examination. The aim of this retrospective, case-controlled study was to identify the correlation between serum albumin concentrations and the prevalence of osteoporosis in postmenopausal patients with RA.MethodsThis study enrolled 197 patients who underwent dual-energy X-ray absorptiometry of lumbar spine (LS) and proximal femur without osteoporosis treatment [mean age, 67.5 years; disease duration, 12.8 years; Disease Activity Score assessing 28 joints with C-reactive protein, 2.0; prednisolone dose, 4.9 mg/day (usage, 42.6%); and LS T-score, ?1.9]. Patients were classified into 2 groups: osteoporosis, defined as ≥ 1 part bone mineral density T-score ≤ ?2.5 or history of fragility fracture of the vertebra or proximal femur (121 patients), and non-osteoporosis (76 patients). Groups were then matched by propensity score using clinical backgrounds affecting bone metabolism.ResultsIn non-matched model, serum albumin concentration was significantly associated with osteoporosis-related factors such as aging, inflammation, physical disability, and glucocorticoid dose. Multivariate logistic regression revealed that serum albumin concentration was independently and significantly associated with osteoporosis risk (odds ratio = 0.22, 95% confidence interval = 0.08, 0.61, p = 0.0033). After propensity score matching, 57 patients for each group showed that in addition to the LS and femoral neck T-scores (p < 0.001), serum albumin concentrations (p = 0.01) remained lower in the osteoporosis group compared to non-osteoporosis group. Receiver operating characteristic curve analysis in non-matched model revealed that when cut-off value of serum albumin concentration for indicating osteoporosis was set at 4.2 g/dl, the area under the curve was 0.69, sensitivity 0.74, and specificity 0.58.ConclusionsLow serum albumin concentration was significantly and independently associated with the prevalence of osteoporosis, which may be considered as one of the osteoporosis-related factors in postmenopausal patients with RA.     

Osteoclast differentiation from circulating mononuclear precursors in Paget's disease is hypersensitive to 1,25-dihydroxyvitamin D(3) and RANKL

A characteristic feature of Paget's disease is an increase in the number of osteoclasts in bone. Osteoclasts are formed from mononuclear phagocyte precursors that circulate in the monocyte fraction of peripheral blood. These cells require the presence of RANK ligand (RANKL)-expressing osteoblastic cells and human macrophage colony-stimulating factor (M-CSF) to form osteoclasts in vitro. To determine the role of osteoclast differentiation from circulating precursors in Paget's disease, we cultured monocytes from Paget's patients and gender- and age-matched normal controls with no evidence of bone disease for up to 21 days in the presence of UMR 106 cells and various concentrations of M-CSF (1-25 ng/mL) and 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] (10(-10) to 10(-7) mol/L). Relative to controls, there was a significant increase in the extent of osteoclast differentiation from pagetic monocytes as assessed by expression of tartrate-resistant acid phosphatase (TRAP), vitronectin receptor (VNR), and lacunar bone resorption. Serial dilution experiments (2 x 10(5) to 2 x 10(2) cells/well) showed no difference in the concentration of osteoclast precursors in the peripheral blood. In Paget's patients with high serum alkaline phosphatase (sAP) levels, increased sensitivity to the osteoclastogenic effect of 1,25(OH)(2)D(3) was noted. Osteoclast differentiation did not occur when M-CSF was substituted by interleukin-6 (IL-6) and soluble IL-6 receptor (sIL-6R), and these factors did not stimulate osteoclast differentiation in the presence of M-CSF. In this in vitro coculture system, osteoclast formation was inhibited by osteoprotegerin in a dose-dependent manner. In the presence of RANKL (5-30 ng/mL) and M-CSF (25 ng/mL), osteoclast formation and bone resorption were significantly increased in cultures of monocytes from patients with high and low sAP levels as compared with normal controls. Our findings suggest that the increase in osteoclast numbers seen in Paget's disease results not from an increase in the number of circulating precursors in peripheral blood but rather from an increased sensitivity of osteoclast precursors to the humoral factors, 1,25(OH)(2)D(3) and RANKL, which regulate osteoclast formation.     

Serum levels of type IIA procollagen amino terminal propeptide (PIIANP) are decreased in patients with knee osteoarthritis and rheumatoid arthritis

OBJECTIVE: The aim of this study was to develop a specific immunoassay for PIIANP and measure its serum concentration in healthy controls and in patients with osteoarthritis (OA) and rheumatoid arthritis (RA). In addition, we investigated circulating forms recognized by antiserum IIA in pools of serum from healthy adults, patients with OA and patients with RA. DESIGN: Using as immunogen and standard the recombinant human Glutathione S-Transferase (GST)-exon 2 fusion protein of type II collagen, we developed a competitive polyclonal antibody-based ELISA. We compare serum PIIANP levels in 43 patients with knee OA (23 women and 20 men; mean age: 62.6+/-9.6 yr), 63 women with RA (mean age: 54+/-16 yr) and 88 healthy controls (67 women, mean age: 53+/-13 yr and 21 men, mean age: 63+/-7 yr). We randomly selected serum in each group for analyze circulating forms. RESULTS: The immunoassay we developed demonstrated adequate intra and inter-assay precision (CV<10%) and dilution recovery (mean: 96%), allowing accurate measurements of serum PIIANP from 1.13 to 40 ng/ml. No significant cross-reactivity of the ELISA was observed with purified intact human procollagen type I N-propeptide, circulating thrombospondin and von Willebrand factor, proteins which exhibit significant sequence homology with PIIANP. Western blot analysis showed that antiserum IIA recognized two circulating immunoreactive forms of approximately 80 and 100 KDa respectively in serum from healthy adults, patients with OA and RA but also in a pool of synovial fluids from patients with OA. Serum PIIANP levels were markedly decreased in patients with knee OA (12.0+/-3.2 vs 25.8+/-7.5 ng/ml for OA and controls respectively, P<0.0001) and RA (14.1+/-2.5 ng/ml vs 21.7+/-7.6 ng/ml for RA and controls respectively, P<0.0001). In patients with RA, serum PIIANP levels were higher in those taking low-dose prednisone compared to non-users (15.0+/-2.4 vs 13.5+/-2.4 ng/ml, P<0.05). CONCLUSIONS: We have developed the first specific immunoassay for serum PIIANP which exhibits adequate technical performances. This assay detects specifically two immunoreactive forms both in healthy adults and patients with arthritis and does not cross react with other proteins with sequence homology with PIIANP. Levels of PIIANP were significantly decreased in patients with knee OA and RA suggesting that type IIA collagen synthesis may be altered in these arthritic diseases. The measurement of type IIA collagen synthesis with this new molecular marker may be useful for the clinical investigation of patients with joint diseases.     

Cementless acetabular replacement in patients with rheumatoid arthritis: a 6- to 14-year prospective study

Sixty-three consecutive patients who had 82 Harris-Galante porous acetabular cups (HGP1) (Zimmer Inc, Warsaw, IN) implanted for the treatment of rheumatoid arthritis were prospectively assessed since 1986. At last examination, 12 patients (16 hips) had died, and 1 patient (1 hip) was lost to follow-up. A total of 65 hips in 50 patients were available for the latest review. The follow-up period was 6.8 years to 14 years (mean, 9.1 years). There had been 6 revisions: 1 for deep infection and 5 for polyethylene cup wear. Survivorship analysis for all failures estimated that 75% of hips would still be revision-free after 4558 days (12.5 years). Polyethylene wear has been identified in a further 7 cases at last examination. The average linear cup wear per year was 0.05 mm(range, 0.00-0.66 mm). There were no cases of acetabular loosening or acetabular migration. These results demonstrate the excellent durability of fixation of the HGP1 cups in patients with rheumatoid arthritis. However, a 32-mm head should probably not be used with this cup given the high associated incidence of polyethylene wear.     

The Souter-Strathclyde elbow replacement in rheumatoid arthritis. 13 patients followed for 5 (1-9) years.

13 Souter-Strathclyde unconstrained elbow prostheses for rheumatoid arthritis were followed for 5 (1-9) years. Pain relief was achieved in all the patients. Flexion-extension was increased by 22 degrees, and pronation/supination by 27 degrees. There were no infections. Three humeral components were radiographically loose, but no patient had any symptoms. One patient sustained a fracture of the distal humeral epicondyle, two patients developed neuropathies and one patient had a postoperative dislocation that needed treatment with an external Hoffman fixator.     

类风湿关节炎患者血清骨代谢标志物水平及炎症因子变化研究

目的探讨类风湿关节炎(rheumatoid arthritis,RA)患者血清骨代谢标志物水平及炎症因子的变化。方法收集RA患者60例和健康对照者20名,再将60例RA患者按照是否合并骨质疏松(osteoporosis,OP)分为OP组(32例)和非OP组(28例)。采用双能X射线骨密度测量仪测骨密度,酶联免疫吸附法测定外周血清白细胞介素(interleukin,IL)-1β、IL-6、IL-17、I型前胶原N-末端前肽(N-terminal propeptide of type I collagen,PINP)、I型胶原C-末端交联顶端肽(type I collagen cross-linked Ctelopeptide,CTX)水平,并详细记录临床、实验室资料。对两组间计量资料采取独立样本t检验进行比较,采用Pearson积差相关法进行相关性分析。结果 (1)RA组与对照组相比,其骨密度、PINP水平普遍较低(P0.05);CTX、IL-1β、IL-17、IL-6水平普遍较高(P0.05)。(2)与非OP组相比,OP组的年龄、病程、IL-1β、IL-17、IL-6水平普遍较高(P0.05),OP组患者CTX、PINP水平虽然高于非OP组,但差异无统计学意义(P0.05)。(3)RA患者外周血血清中IL-1β与红细胞沉降率(erythrocyte sedimentation rate,ESR)成正相关(r=0.423,P0.05),IL-6与C反应蛋白(C-reactive protein,CRP)、ESR、类风湿关节炎患者病情评价(DAS28评分)成正相关(r=0.473、0.370、0.481,P0.05);IL-17与CRP、ESR、DAS28成正相关(r=0.411、0.367、0.468,P0.05);CTX与疾病活动性指标CRP、ESR、DAS28呈正相关(r=0.536、0.488、0.466,P0.05),与病程呈负相关(r=-0.268,P0.05);PINP水平与各疾病活动性指标间均无相关性(P0.05)。结论 RA患者存在较高的OP发生率,且合并OP患者IL-1β、IL-17、IL-6高于未合并OP患者,RA患者中继发OP作用机制可能与炎症因子IL-1β、IL-6、IL-17相关;CTX和PINP与疾病活动和OP密切相关,测定这两个骨代谢指标能够了解RA患者早期骨破坏程度。     

14-3-3η protein is associated with disease activity and osteoporosis in patients with rheumatoid arthritis

IntroductionThis study was designed to explore the potential association of serum 14-3-3η protein level with disease activity and bone mineral density (BMD) in Egyptian patients with rheumatoid arthritis (RA). Patients were recruited from the outpatient clinic at Mansoura University Hospital.Material and methodsOne hundred eighty-eight patients with RA and 192 matched controls were enrolled. The rheumatoid arthritis activity parameters were evaluated in RA patients. Bone mineral density was measured. Serum levels of 14-3-3η protein and IL-6 were estimated for all participants by enzyme-linked immunosorbent assays (ELISA).ResultsRheumatoid arthritis patients had a significantly higher median serum 14-3-3η protein level compared to matched controls (p ≤ 0.05). Serum level of 14-3-3η protein was significantly correlated with DAS28–ESR (p ≤ 0.05) and serum IL-6 level (p ≤ 0.05). The rheumatoid arthritis-osteoporosis group had significantly higher serum 14-3-3η protein than the RA-osteopenia group and RA-control group. Similarly, the difference of the serum 14-3-3η protein between the RA-osteopenia group and the RA-control group was significant. In the linear regression analysis, the strongest factors that were associated with BMD in RA patients were the serum level of 14-3-3η protein (p ≤ 0.05), IL-6 (p ≤ 0.05) and DAS28–ESR (p ≤ 0.05).ConclusionsSerum level of 14-3-3η protein was significantly elevated in RA patients compared to controls and is significantly correlated with parameters of activity disease. The RA-osteoporosis group had significantly higher serum 14-3-3η protein than the RA-osteopenia group and RA-control group. Serum 14-3-3η protein can be a promising biomarker to reflect RA activity and predict presence of osteoporosis in RA patients.     

Polyuria due to vasopressin V2 receptor antagonism is not associated with increased ureter diameter in ADPKD patients

Background

Tolvaptan, a vasopressin V2 receptor antagonist, has been shown to reduce the rates of growth in total kidney volume (TKV) and renal function loss in ADPKD patients, but also leads to polyuria because of its aquaretic effect. Prolonged polyuria can result in ureter dilatation with consequently renal function loss. Therefore, we aimed to investigate the effect of tolvaptan-induced polyuria on ureter diameter in ADPKD patients.

Methods

70 ADPKD patients were included (51 were randomized to tolvaptan and 19 to placebo). At baseline and after 3 years of treatment renal function was measured (mGFR) and MRI was performed to measure TKV and ureter diameter at the levels of renal pelvis and fifth lumbar vertebral body (L5).

Results

In these patients [65.7 % male, age 41 ± 9 years, mGFR 74 ± 27 mL/min/1.73 m² and TKV 1.92 (1.27–2.67) L], no differences were found between tolvaptan and placebo-treated patients in 24-h urine volume at baseline (2.5 vs. 2.5 L, p = 0.8), nor in ureter diameter at renal pelvis and L5 (4.0 vs. 4.2 mm, p = 0.4 and 3.0 vs. 3.1 mm, p = 0.3). After 3 years of treatment 24-h urine volume was higher in tolvaptan-treated patients when compared to placebo (4.7 vs. 2.3 L, p < 0.001), but no differences were found in ureter diameter between both groups (renal pelvis: 4.2 vs. 4.4 mm, p = 0.4 and L5: 3.1 vs. 3.3 mm, p = 0.4).

Conclusions

Tolvaptan-induced polyuria did not lead to an increase in ureter diameter, suggesting that tolvaptan is a safe therapy from a urological point of view.

     

Urinary nerve growth factor level is increased in patients with interstitial cystitis/bladder pain syndrome and decreased in responders to treatment

OBJECTIVE

To measure urinary nerve growth factor (NGF) levels in patients with interstitial cystitis/bladder pain syndrome (IC/BPS), and to evaluate the role of urinary NGF in predicting the response to treatment, as the clinical diagnosis of IC/BPS is based on subjective symptoms and recent investigations suggest that urinary NGF is increased in patients with IC/BPS.

PATIENTS, SUBJECTS AND METHODS

Urine samples from 122 patients with IC/BPS and 28 normal controls were measured for NGF levels using an enzyme‐linked immunosorbent assay. The diagnosis of IC/BPS was based on bladder pain symptoms and the results of cystoscopic hydrodistension. Patients’ perception of pain was assessed by a visual analogue scale (VAS) and a ‘global’ response assessment after treatment. Urinary NGF levels were further normalized to the concentration of urinary creatinine (NGF/Cr) and compared between control and IC/BPS subgroups at diagnosis and after treatment.

RESULTS

Urinary NGF/Cr levels were very low when the bladder was not distended and significantly elevated with a full bladder in patients with IC/BPS. However, urinary NGF/Cr levels were not correlated with VAS scores or cystometric bladder capacity at diagnosis, or maximum bladder capacity during hydrodistension. Patients who responded to treatment and had an improvement in VAS pain score of ≥2 had significantly lower NGF/Cr levels than nonresponders who had a VAS improvement of <2.

CONCLUSIONS

Patients with IC/BPS had greater urinary NGF/Cr levels than controls. A decrease of urinary NGF level was associated with greater pain reduction and a successful response, suggesting that urinary NGF levels can be a useful biomarker for detecting the severity of the bladder condition in patients with IC/BPS.     

甲状旁腺激素(1-34)和阿仑膦酸钠治疗骨质疏松症合并类风湿关节炎疗效的对比研究

目的比较甲状旁腺激素(parathyroid hormone,PTH)(1-34)和阿仑膦酸钠(alendronate,ALN)治疗骨质疏松症合并类风湿关节炎(rheumatoid arthritis,RA)女性患者的疗效。方法选取98例于2017年2月至2017年11月在我院就诊诊断为骨质疏松症合并RA的绝经后女性患者。按照治疗方案将患者分为PTH组和ALN组,两组患者分别接受特立帕肽或阿仑膦酸钠治疗,观察治疗6个月后两组患者骨密度和骨代谢指标的改变。结果在两组治疗6个月后,腰椎的骨密度较治疗前均有显著增加(P0.05)。与ALN组相比,PTH组治疗6个月腰椎骨密度的平均变化百分比显然更高;而股骨颈骨密度仅在PTH组显著增加。结论甲状旁腺激素(1-34)在短期治疗骨质疏松症合并类风湿女性患者时,效果较阿仑膦酸钠更佳。     

Analysis of cartilage-derived retinoic-acid-sensitive protein (CD-RAP) in synovial fluid from patients with osteoarthritis and rheumatoid arthritis

We have measured the concentration of cartilage-derived retinoic-acid-sensitive protein (CD-RAP) in synovial fluid (SF) from the knees of 49 patients with osteoarthritis (OA) and 79 with rheumatoid arthritis (RA) in order to investigate the correlation between the type of joint disease and level of CD-RAP. The mean concentration of CD-RAP in synovial fluid was significantly higher in OA than in RA. The level of CD-RAP in the group of patients with mild OA was significantly higher than in the moderate or severe groups and that in the group with mild RA was also significantly higher than in the other RA groups and decreased with progression of the disease. Immunohistochemical studies showed expression of CD-RAP in the cytoplasm of chondrocytes in newly-formed fibrocartilage. Since CD-RAP is mainly produced in young and proliferating chondrocytes, our results suggest that the level of CD-RAP in synovial fluid reflects remodelling of articular cartilage and may be used as a marker to estimate objectively the restorative reaction of chondrocytes.     

Lp(a) is increased in hemodialysis patients according to the type of dialysis membrane: a 2-year follow-up study

AIMS: Patients with chronic renal failure treated by hemodialysis develop lipoprotein abnormalities that may contribute to their increased risk ofatherosclerosis. This study shows lipid parameter follow-up procedure according to the type of dialysis membrane in an unselected population of 33 hemodialysis patients. PATIENTS AND METHODS: The study included 33 patients with end-stage renal disease and 110 healthy blood bank donors of Tenon Hospital. Cholesterol and triglycerides were determined by enzymatic methods, apoA-I, apoB by immunoturbidimetry and Lp(a) by immunonephelemetry. Apo(a) phenotyping was performed by agarose gel electrophoresis followed by immunoblotting. Patients and controls subjects were estimated by Student's t- and chi2-tests. RESULTS: Patients dialyzed with low-flux membranes had Lp(a) concentrations higher than patients dialyzed with high-flux membranes. Patients dialyzed with polyacrylonitrile membranes (AN 69) had an apoA-I concentration significantly lower than patients dialyzed with hemophane or polysulfone membranes. We also confirmed some of the lipid abnormalities and high Lp(a) concentrations in ESRD patients. CONCLUSION: These results may contribute to a more rational choice of the dialysis membrane in hemodialysis patients.     

Comparison of standard and acupuncture methods of transcutaneous electric nerve stimulation (TENS) in patients with rheumatoid arthritis

The comparison of standard high frequency (ST-TENS) and acupuncture-like TENS (AL-TENS) in patients with rheumatoid arthritis is presented. Thirty-three patients (26 women and 7 men) with rheumatoid arthritis (according to modified ACR criteria), and with the duration of the disease 10.7 +/- 8.8 years are investigated. Each subject received ST-TENS (75 Hz) at the selected joint and AL-TENS (4 Hz) at the contralateral joint respectively. No significant difference between left and right side in pre-treatment pain was the main criterion for selecting the treated joint. Treatment was performed during 12 days. The initiation, duration, level of hypolgesia (according to Ritchie's pain assessment scale and VAS), patients' global assessment and possible reduction of dosage of analgetics/antirheumatics were measured. There was a significant reduction in pain level on ST-TENS site (48.6%), and on AL-TENS site (40.8%), measured on VAS. Results of Ritchie's index showed significant difference before and after application (for each type of TENS P < 0.05). There was no statistical difference between both types of TENS regarding the reduction of pain level, as well as the initiation of analgesic effect, whilst it was noted a slightly longer, although statistically not significant, hypoalgesic effect of AL-TENS. Patients' global assessment also did not differ relating to ST-TENS and AL-TENS, as well as their opinion on possible dosage reduction of analgetics/antirheumatics. Side effects for both types of TENS were negligible. The findings showed that ST-TENS and AL-TENS provided hypoalgesic effect in the similar degree in patients with long-standing rheumatoid arthritis.     

Low level of physical activity in women with rheumatoid arthritis is associated with cardiovascular risk factors but not with body fat mass - a cross sectional study

Background  

As many patients with rheumatoid arthritis (RA) have increased fat mass (FM) and increased frequency of cardiovascular diseases we evaluated if total physical activity (MET-hours) had impact on body composition and cardiovascular risk factors in women with RA.