The clinical utility of bone turnover markers in the evaluation of bone disease in patients with haemophilia A and B

Haemophilia A and B have been associated with increased prevalence of low bone mineral density (BMD). However, the utility of bone turnover markers (BTM) remains unknown. The aim of this study was to evaluate bone metabolism in men with haemophilia and to investigate associations between BTM and bone disease. Serum N‐ (NTX‐I), C‐terminal telopeptide of type I collagen (CTX‐I) and tartrate‐resistant acid phosphatase band‐5b (TRAP‐5b), as bone resorption markers, and osteocalcin (OC) and bone‐specific alkaline phosphatase (b‐ALP), as bone formation markers, were assessed. Seventy men with haemophilia A (n = 59) or B (n = 11) were studied. Patients with low BMD had significantly higher b‐ALP concentrations compared with those with normal BMD (12.8 ± 1.60 vs. 9.72 ± 0.58 μg/L, P = 0.009), without any differences in the other BTM. NTX‐I and CTX‐I concentrations were negatively associated with oestradiol levels and hip BMD and positively with human immunodeficiency virus infection, number of affected joints and arthropathy scores. B‐ALP and OC concentrations were negatively associated with hip BMD, severity of haemophilia and fracture history, and positively with the number of affected joints and testosterone concentrations. After multivariate analysis, NTX‐I levels remained negatively associated with oestradiol levels, whereas b‐ALP concentrations negatively correlated with the level of physical activity and positively with the number of affected joints. Increased bone metabolism exists in men with haemophilia and low BMD. Increased b‐ALP levels may identify patients at high risk for fracture. Increased number of target joints, low physical activity and low oestradiol concentrations are independently associated with increased bone metabolism.     

Effects of single‐agent bortezomib as post‐transplant consolidation therapy on multiple myeloma‐related bone disease: a randomized phase II study

This phase II study explored the effects of bortezomib consolidation versus observation on myeloma‐related bone disease in patients who had a partial response or better after frontline high‐dose therapy and autologous stem cell transplantation. Patients were randomized to receive four 35‐day cycles of bortezomib 1·6 mg/m² intravenously on days 1, 8, 15 and 22, or an equivalent observation period, and followed up for disease status/survival. The modified intent‐to‐treat population included 104 patients (51 bortezomib, 53 observation). There were no meaningful differences in the primary endpoint of change from baseline to end of treatment in bone mineral density (BMD). End‐of‐treatment rates (bortezomib versus observation) of complete response/stringent complete response were 22% vs. 11% (P = 0·19), very good partial response or better of 80% vs. 68% (P = 0·17), and progressive disease of 8% vs. 23% (P = 0·06); median progression‐free survival was 44·9 months vs. 21·8 months (P = 0·22). Adverse events observed ≥15% more frequently with bortezomib versus observation were diarrhoea (37% vs. 0), peripheral sensory neuropathy (20% vs. 4%), nausea (18% vs. 0) and vomiting (16% vs. 0). Compared with observation, bortezomib appeared to have little impact on bone metabolism/health, but was associated with trends for improved myeloma response and survival.     

Detection of low bone mass using quantitative ultrasound measurements at calcaneus: comparative study of an Indian rheumatoid arthritis cohort

Background: Low bone mass in an Indian population combined with bone loss secondary to rheumatoid arthritis (RA) would predict high prevalence of osteoporosis in Indian patients with RA. We used quantitative ultrasound (QUS) to assess bone mass in RA patients and compared it with healthy controls. Methods: One hundred patients with RA and 284 randomly selected healthy controls underwent QUS measurement at the heel. Achilles ultrasonometer was used to measure stiffness index (SI) values and T‐scores. Results: Both groups did not differ significantly in proportion of female gender and postmenopausal females. Prevalence of low bone mass in both the healthy population and RA patients was high. Both SI and T‐scores were lower in RA patients and they were significantly reduced in postmenopausal patients; 31% of patients with RA had osteoporosis as compared to 14% of controls. There was no statistically significant correlation between disease duration and T‐scores (r = 0.11, P = 0.26) and disease duration and SI (r = 0.12, P = 0.20). Conclusion: Our study has found that both the healthy population and RA patients had lower bone mass compared to Western studies. Prospective studies are required to establish whether this is associated with fractures and to establish factors responsible for these findings.     

The interferon‐gamma (IFN‐γ) +874T allele reduces the risk of hepatitis B infection in an Asian population

Increasing evidence suggests that polymorphism of the interferon‐gamma (IFN‐γ) gene in the first intron at position +874 may be associated with chronic hepatitis B virus (HBV) infection and/or HBV clearance. However, the results of relevant studies have been inconsistent. To derive a more precise estimation of the association, we performed a meta‐analysis. In total, 10 independent studies including 1661 chronic HBV‐infected patients and 1142 controls were included in this meta‐analysis. In studies following Hardy–Weinberg equilibrium (HWE), a significantly decreased risk of chronic HBV infection was associated with the IFN‐γ + 874TT genotype in the overall population (TT vs AA: odds ratio (OR) = 0.714, 95% confidence interval (CI) = 0.526–0.969, P = 0.031) when compared with a spontaneously recovered population. Subgroup analysis by ethnicity revealed a similar association in Asian individuals (TT vs AA: OR = 0.706, 95% CI = 0.518–0.962, P = 0.028). Moreover, when compared with a healthy control group, the 874T allele was associated with a significant lower risk of chronic HBV infection in the overall populations (TA vs AA: OR = 0.439, 95% CI = 0.193–0.997, P = 0.049; TT + TA vs AA: OR = 0.475, 95% CI = 0.271–0.832, P = 0.009) and in Asian individuals (TA vs AA: OR = 0.862, 95% CI = 0.744–0.999, P = 0.048). In conclusion, the IFN‐γ + 874TT genotype and 874T allele reduce the risk of chronic HBV infection in Asian individuals.     

Measurement of hand bone mineral density in early rheumatoid arthritis using dual energy X‐ray absorptiometry

Aims: The earliest radiological change in rheumatoid arthritis (RA) is periarticular osteopenia, which occurs prior to the appearance of erosions and clinically apparent deformities. The aim of the study was to measure periarticular bone mineral density (BMD) in the hands of patients with early RA, using dual energy X‐ray absorptiomentry (DEXA) and to correlate this with markers of disease activity and radiological progression. Methods: The study population (n = 50) of patients with RA of < 3 years duration underwent measurement of BMD of the non‐dominant hand, femoral neck and lumbar spine and clinical assessment at baseline, 6 and 12 months. Hand radiographs were performed at baseline and 12 months. Thirty age‐ and sex‐matched controls also underwent measurement of BMD of the non‐dominant hand, femoral neck and lumbar spine. Results: Hand BMD correlated strongly with sex, height, weight and lumbar and femoral neck BMD in both RA subjects and controls. Baseline hand BMD in RA subjects correlated with baseline serum C‐reactive protein (r = ?0.36, P = 0.01) and 12‐month radiographic score (r = 0.36, P = 0.02). There were small non‐significant decreases in hand, femoral neck and lumbar spine BMD over the 12‐month period. Conclusion: Hand BMD measurement using DEXA is a reproducible, well‐tolerated procedure that warrants further investigation as a component of routine assessment in early RA.     

Serum levels of tissue inhibitor of metalloproteinase-1 and periarticular bone loss in early rheumatoid arthritis

We investigated the relationship between disease activity, serum biological mediators of joint damage, and periarticular bone loss in inflammatory arthritis. Patients with early inflammatory arthritis were recruited from a dedicated early arthritis clinic. At the time of recruitment, all had clinical evidence of synovitis. Patients were assessed at baseline and at 1-year follow-up. Periarticular and axial bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Serum levels of matrix metalloproteinase 1 and tissue inhibitor of metalloproteinases 1 (TIMP-1) were measured by enzyme-linked immunosorbent assay. A total 38 patients were included in the study. Twenty had rheumatoid arthritis (RA) and 18 had a seronegative spondylarthropathy (SpA). At baseline, periarticular hand BMD measurements were similar in RA and SpA. At 1 year, the mean periarticular hand BMD was significantly lower in RA (p < 0.05). Significant inverse correlations between both the Ritchie articular index and C-reactive protein levels and the change in periarticular hand BMD at 1 year were observed in RA (r = −0.792, p < 0.001 and r = −0.478, p = 0.045, respectively). Baseline TIMP-1 levels correlated with the change in periarticular hand BMD at 1 year in RA (r = 0.519, p = 0.02). At 1 year, radiographic measures of joint damage were highest in RA. Inverse correlations between the change in periarticular hand BMD and the changes in erosion score (r = −0.90, p = 0.04) were observed in patients demonstrating significant periarticular bone loss. Persistent disease activity was associated with increased periarticular bone loss in the hands in patients with RA, consistent with synovitis-mediated periarticular bone loss. The correlation between baseline TIMP-1 levels and periarticular bone loss over 1 year suggests that TIMP-1 may have utility as a biomarker of periarticular bone loss in early RA.     

Lower bone mineral density of forearm in postmenopausal patients with radiographic hand osteoarthritis

The association between clinical parameters and forearm bone mineral density (BMD) in postmenopausal females with radiographic hand OA has not been determined. We investigated the difference in forearm BMD between radiographic hand OA and non-radiographic hand OA, and also the association between clinical parameters of patients and the level of forearm BMD. A total of 180 postmenopausal patients with hand OA were enrolled in this study. We classified them into two groups according to the Kellgren–Lawrence (K–L) radiological grade, one with radiographic hand OA (K–L grade ≥ 2) and the other with non-radiographic OA (K–L grade < 2) as controls. The number of nodal joints, swollen joints and tender joints were determined in the physical examination, and measures of BMD (g/cm²), Australian Canadian (AUSCAN) OA hand index, grip strength, pinch strength, and visual analogue scale (VAS) were also estimated. Patients with radiographic hand OA had lower distal radius BMD when compared with controls (0.35 ± 0.06 vs. 0.40 ± 0.05, P < 0.001). After adjusting for variables such as age, menopausal duration, number of nodal joints, and AUSCAN function index, the difference in BMD between the two groups was also significantly different (0.35 ± 0.04 vs. 0.38 ± 0.04, P < 0.001). For analysis of risk factors for forearm BMD in hand OA, age and K–L OA grade in total hand OA are considered risk factors, whereas age and menopause duration contribute to the forearm BMD in radiographic hand OA patients (P < 0.001, P = 0.002, respectively). The development of osteoporosis at the distal radius in radiographic hand OA is associated with older age (OR = 1.216, P = 0.002), lower BMI (OR = 0.777, P = 0.004) and lower stiffness in the AUSCAN OA index (OR = 0.505, P = 0.003). This study shows that the BMD levels of the distal radius in patients with radiographic hand OA are significantly lower when compared to those of controls. Forearm BMD levels are positively associated with age and K–L radiological grade in total hand OA, whereas age and menopausal duration are closely related with radiographic hand OA. The presence of osteoporosis in the distal radius in radiographic hand OA may be influenced by age, BMI, and stiffness on the AUSCAN index.     

Association between dietary glycemic index and glycemic load,insulin index and load with incidence of age-related cataract: Results from a case-control study

AimTo identify the association between the dietary carbohydrate indexes, such as dietary glycemic index (DGI) and load (DGL), dietary insulin index (DII) and load (DIL), with the possibility of cataract.MethodThis case–control study consisted of 101 new cases of cataract and 202 controls. DGI and DGL were computed through DGI values previously published. DII was also calculated based on dietary insulin index data published previously.ResultsThere was a significant positive association between the highest quartiles of DGI (OR = 6.56; 95% CI = 2.67–16.06; P < 0.001), DGL (OR = 6.17; 95% CI = 1.93–19.37; P = 0.002) and DIL (OR = 4.17; 95% CI = 1.41–12.27; P = 0.004) with risk of cataract, compared to those on the lowest quartile, but not for DII (OR = 0.85; 95% CI = 0.39–1.86; P = 0.82). Furthermore, after stratifying groups by BMI, a significant direct association between highest quartile of DGI (OR = 6.76; 95% CI = 2.49–18.38; P < 0.001) and DGL (OR = 3.45; 95% CI = 0.96–12.37; P = 0.05) with risk of cataract was evident in individuals with elevated BMI (BMI≥25).ConclusionWe found a significant, direct, relationship between DGI, DGL and DIL with risk of cataract. However, the association between DII and the risk of cataract was not significant, even after adjusting for related confounders.     

Melatonin improves bone mineral density at the femoral neck in postmenopausal women with osteopenia: a randomized controlled trial

Melatonin is known for its regulation of circadian rhythm. Recently, studies have shown that melatonin may have a positive effect on the skeleton. By increasing age, the melatonin levels decrease, which may lead to a further imbalanced bone remodeling. We aimed to investigate whether treatment with melatonin could improve bone mass and integrity in humans. In a double‐blind RCT, we randomized 81 postmenopausal osteopenic women to 1‐yr nightly treatment with melatonin 1 mg (N = 20), 3 mg (N = 20), or placebo (N = 41). At baseline and after 1‐yr treatment, we measured bone mineral density (BMD) by dual X‐ray absorptiometry, quantitative computed tomography (QCT), and high‐resolution peripheral QCT (HR‐pQCT) and determined calciotropic hormones and bone markers. Mean age of the study subjects was 63 (range 56–73) yr. Compared to placebo, femoral neck BMD increased by 1.4% in response to melatonin (P < 0.05) in a dose‐dependent manner (P < 0.01), as BMD increased by 0.5% in the 1 mg/day group (P = 0.55) and by 2.3% (P < 0.01) in the 3 mg/day group. In the melatonin group, trabecular thickness in tibia increased by 2.2% (P = 0.04), and volumetric bone mineral density (vBMD) in the spine, by 3.6% (P = 0.04) in the 3 mg/day. Treatment did not significantly affect BMD at other sites or levels of bone turnover markers; however, 24‐hr urinary calcium was decreased in response to melatonin by 12.2% (P = 0.02). In conclusion, 1‐yr treatment with melatonin increased BMD at femoral neck in a dose‐dependent manner, while high‐dose melatonin increased vBMD in the spine. Further studies are needed to assess the mechanisms of action and whether the positive effect of nighttime melatonin will protect against fractures.     

Association of suppressor of cytokine signalling 3 polymorphisms with insulin resistance in patients with chronic hepatitis C

Suppressor of cytokine signalling 3 is thought to be associated with insulin resistance in patients with chronic hepatitis C. We evaluated the role of suppressor of cytokine signalling 3 polymorphisms in determining insulin resistance in patients with chronic hepatitis C. Two hundred and ninety untreated hepatitis C virus‐infected patients without diabetes and cirrhosis were genotyped for the SNPs rs4969168, rs4969170 and rs12952093 of suppressor of cytokine signalling 3 using the TaqMan Genotyping Assay. We found that the rs4969170 AA genotype and rs4969170 A allele frequency were significantly more common in the insulin‐resistant group than the non‐insulin‐resistant group (89.5% vs 76.1%, OR = 2.693, 95% CI: 1.221‐5.939, P = 0.012 and 94.8% vs 88.0%, OR = 2.463, 95% CI: 1.151–5.271, P = 0.017, respectively). Haplotype G‐C was likely associated with non‐insulin resistance (adjusted P = 0.011). Multiple logistic regression analysis indicates that the independent risk factors for insulin resistance are the SNP rs4969170 AA genotype (OR = 3.005, 95% CI: 1.194–7.560, P = 0.019), HCV genotype 1 (OR = 2.524, 95% CI: 1.099–5.794, P = 0.029) and BMI (OR = 0.514, 95% CI: 0.265–0.999, P = 0.05).     

Relationship between bone mineral density and duration of rheumatoid arthritis

BackgroundLonger disease duration is believed to be associated with more pronounced bone loss in rheumatoid arthritis (RA). This study was designed to assess bone mineral density (BMD) status in RA compared with age-matched control in relation to disease duration.MethodsThis study included 177 RA and 283 age-matched non-RA controls. BMD at the femoral neck and lumbar spine was assessed by Dual Energy X-ray Absorptiometry Osteoporosis was diagnosed according to WHO criteria. We divided patients with RA into groups based on disease duration of <2, 2–5, 5–10, and >10 years and compared them with controls. The relationship between disease duration and BMD was investigated by chi square and Spearman test.ResultsMean age of patients and control subjects was 51.2 ± 12.5 and 52.2 ± 6.7 years, respectively and mean disease duration was 86.5 ± 73.3 months. Osteoporosis at the femoral neck and lumbar spine in patients with RA was significantly higher than in controls. Femoral neck BMD in RA was negatively correlated with disease duration and 4.5% variations of femoral neck BMD was explained by disease duration (r² = 0.045, P = 0.005). Odds Ratio (OR) for osteoporosis in RA patients as compared to controls was increased by prolongation of disease duration from 2.38 (0.38–14.7) in patients with disease duration <2 years to 12.56 (2.24–70.2) in patients with disease duration >10 years. For patients treated with methotrexate compared to those who had never received methotrexate the odds ratio for femoral neck osteoporosis reduced by 64% (OR = 0.36, 95% CI, 0.15–0.91).ConclusionThere is a significant negative relationship between femoral neck BMD and disease duration in RA. The value of OR increases proportionately with lengthening of disease duration which can be reduced significantly by methotrexate therapy.     

Peripheral quantitative computed tomography (pQCT) reveals alterations in the three‐dimensional bone structure in children with haemophilia

Children with haemophilia are at risk of suboptimal bone mass accrual and low bone mineral density (BMD). We recently demonstrated that although BMD in Finnish children with haemophilia was within the normal range, their whole body BMD was significantly lower and hypercalciuria more prevalent than in controls. This study sought to determine the bone structure and strength in physically active children with haemophilia. To investigate the underlying mechanisms in this group, we conducted a case–control study to assess bone structure and strength by peripheral quantitative computed tomography (pQCT) at the radius. The study group comprised 29 patients (mean age 12.2 years) and 46 age‐matched controls. Children with haemophilia had decreased total BMD Z‐score at the distal radius (P ≤ 0.001), but increased cortical bone density at the proximal radius (P ≤ 0.001). Total bone area at the proximal radius was significantly lower in children with haemophilia (P = 0.002), whereas there were no differences in cortical bone area or in polar Strength‐Strain Index, a parameter of bone strength, between the patients and controls. Patients with mild to moderate haemophilia and on‐demand treatment had inferior bone strength compared to those with moderate to severe haemophilia and prophylaxis. Our findings suggest altered skeletal development in patients with haemophilia in the radius, resulting in smaller bone size and higher cortical bone density. Importantly, bone strength at the radius appears equal to healthy children. Prophylactic treatment seems to have a beneficial effect on bone health.     

Lack of association between promoter polymorphisms of <Emphasis Type="Italic">HLA</Emphasis>-<Emphasis Type="Italic">G g</Emphasis>ene and rheumatoid arthritis in Korean population

The aim of this study was to determine whether the HLA-G gene was associated with susceptibility to rheumatoid arthritis (RA). Major histocompatibility complex, class I, G (HLA-G) is involved in immunoregulatory processes and particularly in pathogenesis of inflammatory disorders. To investigate possible association between HLA-G and RA, 296 RA patients and 468 healthy controls were enrolled in this study. Two-promoter single-nucleotide polymorphisms (SNPs) (rs1736936, -1202T/C and rs2735022, -586C/T) in HLA-G gene were analyzed using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). For analysis of data, Helixtree software, SNPAnalyzer, SNPStats, and Haploview version 4.2 were used. Multiple logistic regression models (codominant, dominant, and recessive) were performed for odds ratio (OR), 95% confidence interval (CI), and P value. There were no significant differences in distributions of genotypes and haplotypes between RA patients and control subjects. In clinical features of RA, we found differences between C-reactive protein levels (≥0.5 or <0.5 mg/dL) and two-promoter SNPs. Rs1736936 was significant in codominant (P = 0.028, OR = 0.66, 95% CI = 0.45–0.96) and dominant (P = 0.046, OR = 0.58, 95% CI = 0.34–0.99) models. Also, rs2735022 was significant in codominant (P = 0.038, OR = 0.67, 95% CI = 0.46–0.98) and dominant (P = 0.03, OR = 0.55, 95% CI = 0.33–0.94) models. However, these significant associations disappear after Bonferroni correction. Our results suggest that HLA-G promoter polymorphisms may be not associated with the development of RA in Korean population.     

Risk factors for development and progression of atlantoaxial subluxation in Korean patients with rheumatoid arthritis

We sought to evaluate the frequency of cervical spine (C-spine) involvement, and associated risk factors for this disorder and its progression in Korean patients with rheumatoid arthritis (RA). From 1995 to 2008, we recruited patients with RA attending the rheumatology clinic of a single tertiary care hospital, and evaluated 1,120 of the patients who had neck pain for C-spine involvement. A diagnosis of C-spine involvement was made in 28.6% of patients evaluated, and within this group, anterior atlantoaxial subluxation (AAS) and subaxial subluxation were found in 89.7 and 15%, respectively. Of the 1,120 patients, 570 patients were followed for more than 3 years. Comparing the clinical characteristics of 193 patients with C-spine involvement and 377 patients without C-spine involvement, we found the associations with female gender, RA diagnosis at or before age 45, erosive changes in hand or foot radiographs, C-reactive protein levels and erythrocyte sedimentation rates at the time of first visit, and combination disease-modifying anti-rheumatic drug (DMARD) therapy. We found using logistic regression analysis that significant predictors of C-spine involvement included erosion in hand or foot radiographs (OR = 2.22, p = 0.001) and RA diagnosis at or before age 45 (OR = 2.26, p < 0.001). Among 137 patients followed for more than 3 years, for whom at least two consecutive X-rays were available, we observed radiographic progression in 60.4%. Patients with and without radiologic evidence for cervical progression did not differ significantly in clinical characteristics. In conclusion, Korean patients with RA frequently show radiographic evidence for progressive involvement of the cervical spine. Significant risk factors for C-spine involvement may be associated with erosive peripheral joint disease and RA diagnosis at an early age.     

Meta‐analysis of association between cytokine gene polymorphisms and Behcet's disease risk

The aim of this study was to perform a meta‐analysis of eligible studies to derive precise estimation of the association of interleukin‐1 (IL‐1), IL‐10 and tumor necrosis factor (TNF)‐α polymorphisms with Behcet's disease (BD). Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. A total of 4003 cases and 4748 controls in 19 eligible studies were included in the meta‐analysis. We examined the relationship between seven single nucleotide polymorphisms (SNPs) in the above‐mentioned three cytokine genes and susceptibility to BD. Meta‐analysis indicated the association between the cytokine gene polymorphisms in all study subjects in the allelic model (TNF‐α ‐308A/G: OR = 0.73, 95% CI: 0.61–0.88, P = 0.001; IL‐10 ‐819C/T: OR = 0.72, 95% CI: 0.66–0.78, P < 0.001; IL‐10 ‐592C/A: OR = 0.74, 95% CI: 0.64–0.86, P < 0.001); the dominant model (TNF‐α ‐308A/G: OR = 0.77, 95% CI: 0.64–0.92, P = 0.004; IL‐10 ‐1082G/A: OR = 1.64, 95% CI: 1.10–2.44, P = 0.014); the recessive model (TNF‐α ‐308A/G: OR = 0.27, 95% CI: 0.12–0.65, P = 0.003; IL‐10 ‐819C/T: OR = 0.71, 95% CI: 0.57–0.90, P = 0.004). However, no significant evidence for the associations of IL‐1α ‐889C/T, IL‐1β ‐551C/T, IL‐1β ‐3962C/T polymorphisms with BD susceptibility was detected. The present study might suggest that TNF‐α ‐308A/G, IL‐10 ‐1082G/A, ‐819C/T, ‐592C/A polymorphisms are associated with BD susceptibility.     

Polymorphism of glutathione S-transferase Omega gene: association with risk of childhood acute lymphoblastic leukemia

Purpose  To evaluate the association between glutathione S-transferase Omega (GSTO) genes polymorphism and the susceptibility of acute lymphoblast leukemia (ALL). Methods  The polymorphism of GSTO1 and GSTO2 genes were analyzed in 99 ALL patients compared with 100 healthy children by PCR-based restriction fragment length polymorphism (RFLP) analysis. Results   GSTO1*A140D polymorphism was significantly associated with susceptibility to ALL (OR = 2.24, 95% CI = 1.16–4.35, P = 0.009) whereas, GSTO2*N142D genotype was significantly interacted with high risk group of childhood ALL (OR = 5.52, 95% CI = 1.72–17.71, P = 0.004). Conclusion  This study revealed gene polymorphism in glutathione S-transferase Omega class may be a risk factor to the development of acute childhood lymphoblastic leukemia.     

Association of HLA-E*01:01/*01:03 polymorphism with methotrexate-based treatment response in South Indian rheumatoid arthritis patients

ObjectivesNon-classical HLA-E molecules may influence the disease susceptibility and phenotype including treatment response in chronic inflammatory disorders such as Rheumatoid Arthritis (RA) by virtue of their capacity to modulate innate immune processes. This study was carried out to investigate the role of HLA-E polymorphism in RA susceptibility, clinical and serological phenotype as well as treatment response.MethodsGenomic DNA from 221 RA patients and 200 healthy controls (HC) were typed for HLA-E rs2844724 (C/T) and rs1264457 (HLA-E*01:01/*01:03) single nucleotide polymorphisms (SNPs) using the TaqMan 5'nuclease assay consisting of allele-specific fluorogenic oligonucleotide probes.ResultsOur study did not find any association between HLA-E polymorphism and RA susceptibility or disease phenotype. However, it was observed that the frequency of HLA-E*01:03 allele was higher in all RA cases (Pc = 0.03, OR = 3.02, 95% CI = 1.06–9.39), young onset RA (YORA) (Pc = 0.03, OR = 3.20, 95% CI = 1.11–9.98) and female RA (Pc = 0.04, OR = 3.04, 95% CI = 1.06–9.46) patients who responded well (good responders) to a combination of non-biological disease modifying anti rheumatic drugs (DMARDs), methotrexate (MTX) and hydroxychloroquine (HCQ) as compared to non-responders. Moreover, the frequency of rs2844724 T allele and TT genotype was observed to be higher in patients with low titers of rheumatoid factor (RF) than those with high titers (90% vs. 77% and 79% vs. 59% respectively), although the difference did not reach statistical significance.ConclusionThe results of our study suggest that HLA-E rs1264457 may influence the patient response to treatment with methotrexate-based DMARD therapy. Thus, it may be a useful genetic marker for treatment response in patients with RA.     

Symptoms of depression in people with impaired glucose metabolism or Type 2 diabetes mellitus: The Hoorn Study

Objective To study the prevalence and risk factors of depressive symptoms, comparing subjects with normal glucose metabolism (NGM), impaired glucose metabolism (IGM) or Type 2 diabetes mellitus (DM2). Research design and methods Cross‐sectional data from a population‐based cohort study conducted among 550 residents (276 men and 274 women) of the Hoorn region, the Netherlands. Levels of depressive symptoms were measured using the Centre for Epidemiologic Studies Depression Scale (CES‐D score ≥ 16). Glucose metabolism status was determined by means of fasting and post‐load glucose levels. Results The prevalence of depressive symptoms in men with NGM, IGM and DM2 was 7.7, 7.0 and 15.0% (P = 0.19) and for women 7.7, 23.1 and 19.7% (P < 0.01), respectively. Depression was significantly more common in women with IGM [odds ratio (OR) = 3.60, 95% confidence interval (CI) = 1.57 to 8.28] and women with DM2 (OR = 3.18, 95% CI = 1.31 to 7.74). In men, depression was not associated with IGM (OR = 0.90, 95% CI = 0.32 to 2.57) and non‐significantly more common in DM2 (OR = 2.04, 95% CI = 0.75 to 5.49). Adjustment for cardiovascular risk factors, cardiovascular disease and diabetes symptoms reduced the strength of these associations. Conclusions Depressive symptoms are more common in women with IGM, but not men. Adjustment for cardiovascular risk factors, cardiovascular disease and diabetes symptoms partially attenuated these associations, suggesting that these variables could be intermediate factors.     

Reduced bone density in patients on long‐term warfarin

Aim: Vitamin K is an essential factor for carboxylation of bone matrix protein. Low vitamin K may be associated with reduced bone mineral density (BMD). The issue of whether long‐term sodium warfarin therapy as oral anticoagulant that antagonizes vitamin K, results in decreased bone density, is controversial. Our purpose in this study was to assess the effects of warfarin on BMD. Methods: We performed a case control study survey of bone density in 70 patients with rheumatic valvular heart disease ‘mechanical valve replacement’ on long‐term warfarin compared with 103 randomly selected matched controls. Results: There was a marked reduction in BMD (g/cm²) and T‐score of lumbar spine between patients and controls (P = 0.048, 0.005). Duration of warfarin use was the only risk factor of significant importance respectively on spinal T‐score (P < 0.03). Conclusions: Screening of patients on long‐term warfarin for reduced bone density should be considered. We strongly suggest the prophylactic use of calcium–vitamin D supplements for these patients.