Soluble receptor activator of NFkappa B-ligand and osteoprotegerin in rheumatoid arthritis - relationship with bone mineral density,disease activity and bone turnover

The aim of our study was to investigate determinants of bone mineral density (BMD) measured by dual X-ray absorptiometry at the lumbar spine (BMD-LS) and at the femoral neck (BMD-FN) in patients with rheumatoid arthritis (RA) with special respect to bone resorbing proinflammatory cytokines and their physiological antagonists. In 142 RA patients the following parameters were measured in parallel with BMD: serum levels of soluble receptor activator of nuclear factor kappa-B-ligand (sRANKL), osteoprotegerin (OPG), interleukin (IL)-6, soluble glycoprotein 130 (sgp130), 25-hydroxyvitamin D3 (25OHD₃), 1,25-dihydroxyvitamin D3 (1,25[OH]₂D₃), intact parathyroid hormone, osteocalcin, ionized calcium, renal excretion of pyridinolin and deoxypyridinolin, C-reactive protein, and erythrocyte sedimentation rate (ESR). No significant differences of sRANKL, OPG, IL-6, and spg130 were found between patients with osteoporosis (47.9% of patients), osteopenia (36.6%), and normal BMD (15.5%). However, total sRANKL was significantly higher in postmenopausal women with osteoporosis at FN than in those without (p < 0.05) and showed a negative correlation with BMD-LS in patients older than 60 years (p = 0.01). BMD-LS and BMD-FN (p < 0.001) and total sRANKL (p < 0.01) were negatively related with the age of the patients. Only IL-6 (positive correlation, p < 0.001) and 1,25(OH)₂D₃ (negative correlation, p < 0.001) but not sRANKL, OPG, and sgp130 were related to disease activity. Using multiple linear regression analysis, menopause was identified as the crucial negative determinant of BMD-LS (R ² = 0.94, p = 0.001), whereas cumulative glucocorticoid dose (β = −0.80, p = 0.001) and ESR (β = −0.44, p = 0.016) were the negative determinants of BMD-FN (R ² = 0.86, p = 0.001). The results indicate that influences of age and gender must be considered in investigations on the relationship between BMD and sRANKL in RA and that high serum levels of sRANKL seems to be associated with osteoporosis only in subgroups of RA patients.     

Bone mineral density in patients with familial Mediterranean fever

This study was carried out to determine lumbar and femoral bone mineral density (BMD) in patients with familial Mediterranean fever (FMF), an autosomal-recessive disease characterized by recurrent episodes of peritonitis, pleuritis, and arthritis, which are usually associated with fever. In patients with FMF and control subjects, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were measured. BMD was determined at the lumbar spine (L1–4) and the femoral regions (neck and total) using dual energy X-ray absorptiometry. Twenty-eight FMF patients and 30 control subjects without a history of inflammatory disease participated in our study. The demographic variables, such as age, sex and body mass index were similar between patients and controls (P > 0.05). We found statistically significant difference in ESR and CRP between FMF patients and controls (P < 0.01, P < 0.05 respectively). There was statistically significant difference in lumbar spine, femoral neck, and total femur BMD between FMF patients and control groups (P < 0.001, P < 0.01, P < 0.01 respectively).Our study indicates that lumbar spine and femoral neck and total femur BMD in patients with FMF may be lower than in healthy subjects.     

Relationship between soluble markers of immune activation and bone turnover in post-menopausal women with rheumatoid arthritis.

OBJECTIVE: Regarding interactions between pro-inflammatory cytokines and bone metabolism in rheumatoid arthritis (RA), we investigated the relationship between the serum levels of interleukin (IL)-1beta, IL-6, soluble interleukin-2 receptor (sIL-2r), C-reactive protein (CRP), the vitamin D metabolites 25-hydroxyvitamin D3 (25OHD3) and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], intact parathyroid hormone (iPTH) as well as serum and urinary parameters of bone turnover in 74 post-menopausal women with RA. RESULTS: SIL-2r correlated negatively with 1,25(OH)2D3 (P < 0.01), whereas IL-6 showed a positive correlation with urinary excretion of deoxypyridinoline collagen cross-links (P < 0.01). 1,25(OH)2D3 (P < 0.01) and iPTH (P < 0.01) were negatively related to CRP, whereas the urinary excretion of pyridinoline (P < 0.01) and deoxypyridinoline (P < 0.01)-collagen cross-links showed a positive correlation with CRP. 1,25(OH)2D3 (P < 0.01) and iPTH (P < 0.05) were positively related to bone alkaline phosphatase as a marker of osteoblast function. CONCLUSION: Our data indicate that IL-6 is a critical determinant of increased bone resorption in post-menopausal RA women with high disease activity and that serum levels of 1,25(OH)2D3 are inversely related to T-cell activation.     

Effect of Calcium Carbonate Combined With Calcitonin on Hypercalcemia in Hemodialysis Patients

This short‐term study assessed the efficacy and safety of calcium carbonate combined with calcitonin in the treatment of hypercalcemia in hemodialysis patients. Patients (n = 64) on hemodialysis for chronic kidney disease for more than 6 months were included based on total serum calcium more than 10.5 mg/dL. All patients were randomized (1 : 1) to receive calcium carbonate combined with calcitonin (Group I) or lanthanum carbonate (Group II) for 12 weeks. Blood levels of calcium, phosphorus and intact parathyroid hormone (iPTH) were measured every month, bone mass density (BMD) and coronary artery calcium scores (CACS) were measured at 3 months. During the study period, serum calcium decreased from 10.72 ± 0.39 to 10.09 ± 0.28 mg/dL (P < 0.05), serum phosphorus decreased from 6.79 ± 1.05 to 5.46 ± 1.18 mg/dL (P < 0.05), and serum iPTH levels in the Group I and Group II were not significantly different from the baseline. There were no significant differences in CACS in either group. There were no significant differences in the BMD values between Group I and baseline. In Group II, the BMD values at the lumbar spine and femoral neck were significantly lower than those before the trial and significantly lower than the corresponding values of Group I (P < 0.05). Calcium carbonate combined with calcitonin and lanthanum carbonate were equally effective in the suppression of hypercalcemia in hemodialysis patients. There were no serious treatment‐related adverse events in treatment with calcium carbonate combined with calcitonin.     

The study of bone mineral density and bone turnover markers in postmenopausal women with active rheumatoid arthritis

The aim of this study was to investigate determinants of reduced bone mineral density (BMD) in postmenopausal women with active rheumatoid arthritis (RA) and to evaluate whether there are common markers of bone loss. We evaluated BMD of the femoral neck using dual-energy X-ray absorptiometry, and the measured biochemical markers included serum bone-specific alkaline phosphatase (BALP), serum osteocalcin (OC), and serum cross-linked N-telopeptidases of type I collagen (NTx). Serum BALP and NTx concentrations were measured by enzyme-linked immunsorbent assay, and OC was measured using an immunoradiometric assay. One hundred and forty postmenopausal Japanese women who had not received treatment with bisphosphonates or hormone replacement therapy were entered into the study. Thirty-four patients (41.0%) had femoral osteopenia (T score −1 to −2.5) and 23 patients (27.7%) had osteoporosis (T < −2.5). The body mass index of patients with normal BMD (T score ≥ −1.0) was significantly higher (P < 0.01) than in patients with osteoporosis at the femoral neck. The T score exhibited a significant negative correlation with age and the duration of RA disease. Serum BALP and serum OC, markers of osteoblast function, were negatively related to erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and matrix metalloproteinase-3 (MMP-3). However, serum NTx, a marker of resorptive function, exhibited a positive correlation with ESR, CRP, and MMP-3. From these results, this study suggests that generalized bone loss occurs in active RA and is characterized by evidence of bone resorption that is correlated with the high levels of inflammation. Body mass index, disease duration, and high serum NTx level were common risk factors in osteoporosis of postmenopausal women with RA.     

The study of bone mineral density and bone turnover markers in postmenopausal women with active rheumatoid arthritis

Abstract

The aim of this study was to investigate determinants of reduced bone mineral density (BMD) in postmenopausal women with active rheumatoid arthritis (RA) and to evaluate whether there are common markers of bone loss. We evaluated BMD of the femoral neck using dual-energy X-ray absorptiometry, and the measured biochemical markers included serum bone-specific alkaline phosphatase (BALP), serum osteocalcin (OC), and serum cross-linked N-telopeptidases of type I collagen (NTx). Serum BALP and NTx concentrations were measured by enzyme-linked immunsorbent assay, and OC was measured using an immunoradiometric assay. One hundred and forty postmenopausal Japanese women who had not received treatment with bisphosphonates or hormone replacement therapy were entered into the study. Thirty-four patients (41.0%) had femoral osteopenia (T score ?1 to ?2.5) and 23 patients (27.7%) had osteoporosis (T < ?2.5). The body mass index of patients with normal BMD (T score ≥ ?1.0) was significantly higher (P < 0.01) than in patients with osteoporosis at the femoral neck. The T score exhibited a significant negative correlation with age and the duration of RA disease. Serum BALP and serum OC, markers of osteoblast function, were negatively related to erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and matrix metalloproteinase-3 (MMP-3). However, serum NTx, a marker of resorptive function, exhibited a positive correlation with ESR, CRP, and MMP-3. From these results, this study suggests that generalized bone loss occurs in active RA and is characterized by evidence of bone resorption that is correlated with the high levels of inflammation. Body mass index, disease duration, and high serum NTx level were common risk factors in osteoporosis of postmenopausal women with RA.     

The effect of rheumatoid arthritis and steroid therapy on bone density in postmenopausal women

Objective. To assess bone mineral density (BMD) in postmenopausal women with rheumatoid arthritis (RA) and the relative effects of disease activity, disability, and past and current use of corticosteroids. Methods. One hundred ninety-five postmenopausal patients with RA were compared with 597 postmenopausal control subjects. Bone density was measured at the lumbar spine and the proximal femur using dual x-ray absorptiometry. Patients were divided into 3 groups according to corticosteroid use, i.e., never users (61%), current users (21%), and ex-users (18%). Results. Compared with controls, the never users had no difference in BMD at the lumbar spine, but a 6.9% reduction at the femur (95% confidence interval [95% CI] 3.4–10.3%). In current users (mean daily prednisolone dosage 6.9 mg), BMD was reduced by 6.5% at the spine (95% CI 0–13.0%) and by 7.4% at the hip (95% CI 1.2–13.6%) compared with never users, after adjustment for age, weight, duration of menopause, and functional disability. Mean BMD was similar in the ex-user and never user groups. Results were confirmed in 54 patients who had whole-body BMD measurements. There were inverse correlations between BMD and Health Assessment Questionnaire scores (femoral BMD r = –0.23, P < 0.01; whole-body BMD r = –0.40, P < 0.01) and between BMD and cumulative steroid dose (femoral BMD r = –0.32, P < 0.01; whole-body BMD r = –0.72, P < 0.01). Conclusion. Osteoporosis in postmenopausal women with RA is more evident at the hip than the spine, and the most important determinants of bone loss are disability and cumulative corticosteroid dose. Low-dose steroids cannot be used with complacency, but recovery after discontinuation of use may be possible.     

Doppler sonographic comparative study on usefulness of synovial vascularity between knee and metacarpophalangeal joints for evaluation of articular inflammation in patients with rheumatoid arthritis treated by infliximab

We used Doppler sonography to evaluate the therapeutic effects of infliximab on the knee and metacarpophalangeal (MCP) joints of 10 patients with rheumatoid arthritis (RA), based on the color flow signals (CFS) and resistance index (RI) of synovial vascularity. After three injections of infliximab, we observed significant improvement in numbers of tender joints (P < 0.01), values of C-reactive protein (CRP) (P < 0.01), erythrocyte sedimentation rate (ESR) (P < 0.001), disease activity scores including tender joints, swollen joints, and ESR (DAS28-E3) (P < 0.0001), and CFS of knee (P < 0.001) and MCP (P < 0.05) joints. There was no significant improvement in RI values of knee or MCP joints after the therapy. We observed significant correlation between CFS of knee joints (knee-CFS) and values of CRP (P < 0.01), ESR (P < 0.01), and DAS28-E3 (P < 0.05), but not between CFS of MCP joints (MCP-CFS) and values of CRP, ESR, and DAS28-E3. However, no significant correlation was observed between 10 difference values (before values–after values) of CFS grades of knee or MCP joints and 10 difference values each of CRP, ESR, or DAS28-E3. The knee joints are more suitable than MCP joints for obtaining CFS in Doppler sonography, and are more useful than MCP joints for evaluation.     

Does low-dose and short-term glucocorticoids treatment increase the risk of osteoporosis in rheumatoid arthritis female patients?

Rheumatoid arthritis (RA) is frequently complicated by peri-articular and generalized osteoporosis due to increased bone resorption by activated osteoclasts. Pro-inflammatory cytokines, such as TNF-alpha, interleukin 1 (IL1), and interleukin 6 (IL6) are thought, among other factors, to be directly responsible for this extra-articular complication of RA. Glucocorticoids (GCS) commonly prescribed in RA due to their strong anti-inflammatory effect are also well known for causing secondary osteoporosis during a prolonged use. An influence of low-dose GCS therapy (8.7 mg per day) on a bone turnover in female RA patients with or without previous history of GCS treatment was investigated by measuring bone mineral content (BMC), bone mineral density (BMD), and various biochemical markers of inflammation and bone metabolism in comparison to results obtained from: (1) RA patients who have not been treated with GCS and (2) the control group of healthy individuals. Sixty-two female patients with established active RA and 178 healthy individuals from the control group have been investigated. The RA patients were divided into three groups: 21 treated with GCS before the trial—these patients have continued GCS therapy using low doses during the observation; 21 with low-dose GCS therapy launched at the beginning of the trial; and 20 left without GCS treatment. All patients have been assessed twice: at the beginning and after 12 months of observation. BMC and BMD have been measured in all patients in a distal part of forearm. Additionally, several different biochemical markers of osteoporosis and inflammation have been determined.We did not notice any increase in bone metabolism between RA patients receiving GCS therapy for the first time and those treated without GCS after 12 months of observation. Results of BMC, BMD osteocalcin level, total and bone alkaline phosphatase, carboxy-terminal collagen cross links, carboxy-terminal propeptides of type 1 collagen, deoxypyridynoline, and calcium/creatinine ratio were comparable in both groups at the end of the study. There was a significant decrease of the level of IL-6 in patients who had GCS therapy launched at the beginning of observation (p < 0.01). However, levels of C-reactive protein (CRP) and α1-acid-glycoprotein (AGP) have not changed; the level of ESR dropped significantly (p < 0.05) in this group. In contrast, in the group of patients with the previous history of prolonged GCS treatment receiving low doses of GCS during the trial, statistically significant increase of CRP and AGP could be observed (p < 0.05) along with further significant worsening of the primary low BMD (p < 0.05).Based on the obtained data, we came to the conclusion that anti-inflammatory effect of the low-dose GCS therapy in RA patients without previous history of their use may balance their direct negative effect on BMC and BMD. In this group of RA patients, benefits resulting from the 12-month GCS therapy prevail over adverse effects, even if calcium with vitamin D3 supplementation, biphosphonians, or estrogens have not been introduced. On the other hand, low-dose GCS therapy could have no benefit for RA patients with the previous history of their prolonged use, as a rise of markers of inflammation and bone turnover, resulting in the further bone loss, has been observed.     

Erosive disease associated with higher bone resorption and lower bone density in women with rheumatoid arthritis

Objective: To evaluate the bone density and bone metabolism in women with rheumatoid arthritis (RA), focusing on disease activity, joint erosion, and RA‐epitope. Methods: Disease activity was assessed using erythrocyte sedimentation rate, C‐reactive protein, rheumatoid factor, Ritchie articular index (RAI), and disease activity score (DAS). The presence of joint erosion was assessed using wrist‐hand and feet X‐ray, and wrist‐hand magnetc resonance imaging. A fasting metabolic bone study was done including serum calcium, phosphate, 25(OH) vitamin D, parathyroid hormone (PTH), alkaline phosphatase (ALP), osteocalcin, and urine deoxypyridinoline/creatinine (DPD/Cr) ratio. Bone mineral density (BMD) was measured at hip, spine, distal forearm, hand, and total body using dual energy X‐ray absorptiometry (DEXA) machine. HLA‐DRB1 genes were examined using DNA sequencing based typing. Results: Seventy‐six women with RA according to 1987 American College of Rheumatology (ACR) criteria with clinical onset equal to or less than 5 years were examined. Mean (SD) of age was 55.4 (13.7) years, disease duration 34.9 (36.4) months, and 96% with ACR functional criteria class I and II. HLA typing demonstrated that 61.4% of them have the RA shared‐epitope (QRRAA or QKRAA or RRRAA) in their HLA‐DRB1 alleles. Most of them had been receiving disease‐modifying antirheumatic drugs and glucocorticoid. Erosive disease was significantly correlated with intertrochanter BMD (P = 0.044), serum calcium (P = 0.005), and urine DPD/Cr ratio (P < 0.001). Patients with erosive disease had higher DAS (P = 0.017), lower serum calcium (P = 0.006), and higher urine DPD/Cr ratio (P < 0.001). There were no statistically significant differences in serum ALP, osteocalcin, 25(OH) vitamin D, and PTH. Patients with erosive disease had lower BMD at all sites including hip, forearm, hand, lumbar spine, and total body, though only statistically significant at intertrochanter (P = 0.042). Bivariate correlation demonstrated that at all sites BMD, except femoral neck and hand BMD, negatively correlated with urine DPD/Cr ratio. Logistic regression model showed that erosive disease was a significant factor for low bone density (T‐score < ?1) at intertrochanter (OR = 6.0; 95% CI = 1.3–27.3; P = 0.020), total hip (OR = 5.5; 95% CI = 1.1–26.8; P = 0.035), and distal radius‐ulna (OR = 3.9; 95% CI = 1.1–14.0; P = 0.041). Conclusion: Patients with erosive disease demonstrated lower BMD, lower serum calcium level, and higher bone resorption. Erosive disease was a significant factor for osteopenia or osteoporosis.     

Doppler sonographic comparative study on usefulness of synovial vascularity between knee and metacarpophalangeal joints for evaluation of articular inflammation in patients with rheumatoid arthritis treated by infliximab

Abstract

We used Doppler sonography to evaluate the therapeutic effects of infliximab on the knee and metacarpophalangeal (MCP) joints of 10 patients with rheumatoid arthritis (RA), based on the color flow signals (CFS) and resistance index (RI) of synovial vascularity. After three injections of infliximab, we observed significant improvement in numbers of tender joints (P < 0.01), values of C-reactive protein (CRP) (P < 0.01), erythrocyte sedimentation rate (ESR) (P < 0.001), disease activity scores including tender joints, swollen joints, and ESR (DAS28-E3) (P < 0.0001), and CFS of knee (P < 0.001) and MCP (P < 0.05) joints. There was no significant improvement in RI values of knee or MCP joints after the therapy. We observed significant correlation between CFS of knee joints (knee-CFS) and values of CRP (P < 0.01), ESR (P < 0.01), and DAS28-E3 (P < 0.05), but not between CFS of MCP joints (MCP-CFS) and values of CRP, ESR, and DAS28-E3. However, no significant correlation was observed between 10 difference values (before values–after values) of CFS grades of knee or MCP joints and 10 difference values each of CRP, ESR, or DAS28-E3. The knee joints are more suitable than MCP joints for obtaining CFS in Doppler sonography, and are more useful than MCP joints for evaluation.     

The treatment of osteoporosis in patients with rheumatoid arthritis receiving glucocorticoids: a comparison of alendronate and intranasal salmon calcitonin

Objective The purpose of this study was to assess the effects of alendronate and intranasal salmon calcitonin (sCT) treatments on bone mineral density and bone turnover in postmenopausal osteoporotic women with rheumatoid arthritis (RA) receiving low-dose glucocorticoids.Methods Fifty osteoporotic postmenopausal women with RA, who had been treated with low-dose corticosteroids for at least 6 months, were randomized to receive alendronate 10 mg/day or sCT 200 IU/day for a period of 24 months. All patients received calcium supplementation 1,000 mg and vitamin D 400 IU daily. Bone mineral density (BMD) of the lumbar spine, femoral neck, and trochanter was measured annually using dual-energy X-ray absorptiometry. Bone metabolism measurements included urinary deoxypyridinoline (DPD), serum bone alkaline phosphatase (BAP), and serum osteocalcin (OC).Results Over 2 years, the lumbar spine (4.34%, P <0.001), femoral neck (2.52%, P <0.05), and trochanteric (1.29%, P <0.05) BMD in the alendronate group increased significantly. The sCT treatment increased lumbar spine BMD (1.75%, P <0.05), whereas a significant bone loss occurred at the femoral neck at month 24 (–3.76%, P <0.01). A nonsignificant decrease in the trochanteric region was observed in the sCT group (–0.81%). The difference between the groups with respect to the femoral neck and trochanteric BMD was statistically significant ( P <0.001and P <0.05, respectively). The decreases in urinary DPD (–21.87%, P <0.001), serum BAP (–10.60%, P <0.01), and OC (–19.59%, P <0.05) values were statistically significant in the alendronate group, whereas nonsignificant decreases were observed in the sCT group (–5.77%, –1.96%, and –4.31%, respectively). A significant difference was found in the DPD and BAP levels between the two treatment groups in favor of the alendronate group at all time points ( P =0.001 and P <0.05, respectively).Conclusion The results of this study demonstrated that alendronate treatment produced significantly greater increases in the femoral neck BMD and greater decreases in bone turnover than intranasal sCT in RA patients receiving low dose glucocorticoids.     

Bone mineral density and frequency of osteoporosis among Vietnamese women with early rheumatoid arthritis

Generalised bone mineral density (BMD) reduction often occurs in established rheumatoid arthritis (RA); however, in early RA, there is a disagreement with regard to BMD in the femoral neck and lumbar spine, and there is no available information for the whole body. Therefore, the aims of this study were to investigate the BMD, frequency of osteoporosis and the risk factors for BMD reduction in Vietnamese women with early RA. BMD in the femoral neck, lumbar spine L1–4 and whole body was measured in 105 women with early RA (disease duration ≤3 years) and 105 age-matched healthy women (26–73 years) using a dual energy X-ray absorptiometry. Femoral neck and whole body BMD in women with RA were lower (p < 0.05) than controls, while lumbar spine BMD was similar between two groups. The frequency of osteoporosis in the femoral neck, lumbar spine and whole body in women with RA aged ≥50 were higher (p < 0.05) than controls: 41.8% versus 29.5%, 42.2% versus 37.7% and 37.1% versus 28%, respectively. There were associations between the frequencies of osteoporosis at all sites with postmenopausal status, glucocorticoid use, rheumatoid factor positivity and disease activity with lumbar spine BMD and disease disability with femoral neck and whole body BMD. In conclusion, women with early RA had significantly lower femoral neck and whole body BMD, but had similar lumbar spine BMD compared with controls. The frequency of osteoporosis at all sites was significantly higher in women with RA than controls, suggesting that assessment of BMD should be considered in women with early RA.     

Associations with subregional BMD-measurements in patients with rheumatoid arthritis

Patients with rheumatoid arthritis (RA) have bone loss to various degrees at different skeletal sites. The subregional bone mineral density (BMD) of the hand and the correlation of BMD to other regional bone losses, parameters of inflammation or bone resorption was evaluated in 421 patients with RA and controls. RA patients had significantly (P < 0.01) lower BMD values in the carpus (0.405 ± 0.004 g/cm²), metacarpal joint II (0.318 ± 0.036 g/cm²) and metacarpal joint III (0.326 ± 0.022 g/cm²) compared to controls. There was no difference in bone density at the lumbar spine or hip. Significant (P < 0.001) correlations were found between BMD total of the hand, its subregions, the forearm and hip. Parameters of inflammation correlated significantly (P < 0.001) with pyridinolines (r = 0.378), desoxypyridinolines (r = 0.183), forearm (r = −10, P < 0.05), MCP II (r = −0.190, P < 0.001), MCP III (r = 0.204, P < 0.001) and carpus (r = 0.191, P < 0.001).     

Early Intervention With Intravenous or Pulse Oral Vitamin D Therapy Is More Effective in the Treatment of Secondary Hyperparathyroidism

The K/DOQI clinical practice guidelines recommend vitamin D therapy should be started when the intact parathyroid hormone (iPTH) exceeds 300 pg/mL in patients with secondary hyperparathyroidism. To examine whether the effect of vitamin D therapy on mineral metabolism and parathyroid gland growth varies according to the stage of secondary hyperparathyroidism and iPTH level, 47 patients with secondary hyperparathyroidism received either intravenous or pulse oral vitamin D therapy. The patients were divided into two groups based on the iPTH level at the start of vitamin D therapy: the P_<300 group (N = 23) with iPTH <300 pg/mL; and the P^≥300 group (N = 24) with iPTH ≥300 pg/mL. We examined serial changes in several serum mineral parameters and parathyroid gland volume and the cumulative incidence of parathyroidectomy in the first two years. Serum calcium, phosphorus, calcium–phosphorus product, and iPTH levels of the P^≥300 group were significantly higher than those of the P_<300 group, and could not be maintained within the target ranges set by the K/DOQI guidelines. In contrast, the serum levels of phosphorus, calcium–phosphorus product, and iPTH were maintained within the target ranges and the parathyroid gland did not enlarge in the P_<300 group. The cumulative incidence of parathyroidectomy in the P^≥300 group was significantly higher than in the P_<300 group. Early intervention with intravenous or pulse oral vitamin D therapy at serum iPTH <300 pg/mL can control serum phosphorus, calcium–phosphorus product, and PTH levels to the target ranges and slow the progression of secondary hyperparathyroidism.     

The balance between soluble receptors regulating IL-6 trans-signaling is predictive for the RANKL/osteoprotegerin ratio in postmenopausal women with rheumatoid arthritis

The objective of this study is to investigate the relationship between soluble components of the interleukin 6 (IL-6) system mediating and modifying IL-6 trans-signaling and the RANKL–RANK–osteoprotegerin system in postmenopausal women with rheumatoid arthritis (RA). The following parameters were investigated in 126 postmenopausal women with RA: IL-6, soluble IL-6-receptor (sIL-6R), soluble glycoprotein 130 (sgp130), sRANKL, osteoprotegerin (OPG), osteocalcin, erythrocyte sedimentation rate and C-reactive protein in sera, pyridinolin and desoxypyridinolin crosslinks in the morning urine. Bone mineral density (BMD) was measured by dual X-ray absorptiometry at the lumbar spine (BMD-LS) and at the femoral neck (BMD-FN). Predictors of RANKL/OPG ratio and BMD were evaluated by multiple linear regression analysis. The following determinants of the RANKL/OPG ratio were identified: sIL-6R/sgp130 ratio and daily glucocorticoid (GC) dose as positive determinants in the whole group (R ² = 0.56; P = 0.001), sIL-6R/sgp130 ratio as the exclusive positive determinant in patients with GC therapy (R ² = 0.48; P = 0.001) and sgp130 as negative determinant in patients without GC (R ² = 0.42; P = 0.031). Sgp130 was highly significantly positively correlated with OPG in the whole group (P < 0.001) as well as in patients with (n = 70; P < 0.05) and without GC therapy (n = 56; P < 0.01). sIL-6R was the main negative predictor of BMD-LS (R ² = 0.41; P = 0.019). High sIL-6R/sgp130 ratio and/or low sgp130 are associated with a high sRANKL/OPG ratio in sera of postmenopausal women with RA indicating the critical significance of IL-6 trans-signaling for an increase in the RANKL/OPG ratio and of bone resorption. Inhibition of IL-6 trans-signaling may be an effective bone-protecting principle in postmenopausal women with RA.     

Markers of bone metabolism in postmenopausal women with rheumatoid arthritis

Objective. To investigate bone metabolism in postmenopausal women with rheumatoid arthritis (RA) treated with or not treated with corticosteroids, and the response to hormone replacement therapy (HRT). Methods. One hundred six RA patients were divided into those taking low-dose steroids (RA+; n = 35) and those not (RA–; n = 71) and randomly allocated to receive HRT or calcium for 2 years. Bone formation markers included serum osteocalcin (OC) and bone-specific alkaline phosphatase, and resorption markers included urinary deoxypyridinoline (DPyr) and CrossLaps (XL). Bone mineral density (BMD) was measured annually using dual x-ray absorptiometry. Results. OC levels were significantly lower in both the RA+ and RA– groups compared with 112 healthy control subjects (P < 0.01 and P < 0.05, respectively), but were similar in the 2 RA groups. DPyr and XL levels were elevated in the RA+ group compared with the RA– group (P < 0.05) but were similar between the RA– group and controls. OC was negatively correlated with parameters of disease activity (P < 0.05). After HRT, XL excretion decreased significantly in the overall RA group. Three-month changes in XL correlated with 2-year changes in spinal BMD (P < 0.01). Conclusion. Bone metabolism may be uncoupled in chronic RA. Bone formation appears to be reduced, partly reflecting disease activity, whereas resorption increased only in steroid users. HRT reduces resorption in RA irrespective of steroid usage, emphasizing its value in the treatment of postmenopausal women with RA.     

Sex hormone status and osteoporosis in postmenopausal women with rheumatoid arthritis

Sex hormones have important effects on bone, especially in postmenopausal women. These hormones may be of particular significance in patients with rheumatoid arthritis (RA), who have a high frequency of osteoporosis. To examine this, we measured estrogen and androgen concentrations and bone mineral density (BMD) in 49 postmenopausal women with RA and 49 normal postmenopausal women. Compared with the controls, postmenopausal RA patients had significantly reduced levels of estrone (median 18 pmoles/liter versus 49; P < 0.001), dehydroepiandosterone sulfate (DHEAS) (median 0.3 μmoles/liter versus 2.0; P < 0.001), testosterone (median 0.6 nmoles/liter versus 0.95; P < 0.001), and femoral BMD (mean 0.72 gm/cm² versus 0.80; P < 0.002). Prednisolone therapy in 22 patients (mean dosage 8 mg/day) was associated with reductions in estrone and testosterone levels; however, DHEAS and femoral BMD were also decreased in RA patients who were not receiving corticosteroids. Reduced DHEAS levels in postmenopausal women with RA may increase their risk of osteoporosis.     

Increased bone mass with pamidronate treatment in rheumatoid arthritis. Results of a three-year randomized,double-blind trial

Objective. Osteoporosis is a frequent complication of rheumatoid arthritis (RA). We therefore investigated the effect of oral pamidronate therapy as a specific bone-sparing agent in RA. Methods. The study design was a 3-year randomized, double-blind trial of 300 mg oral pamidronate/day compared with placebo in 105 RA patients. Bone mineral density (BMD) measured at 12-month intervals was the primary efficacy parameter. Results. In 3 years, lumbar spine and forearm BMD increased significantly in the pamidronate-treated group (by 8.4 ± 6.9% [mean ± SEM] [P < 0.0001] and 5.2 ± 6.5% [P < 0.005], respectively), compared with nonsignificant changes in the placebo-treated patients (increase of 0.6 ± 5.2% and decrease of 1.2 ± 5.8%, respectively). Femoral neck BMD increased in the pamidronate-treated group (by 2.6 ± 8.6%) and decreased significantly in the placebo-treated group (by 4.0 ± 1.3% [P < 0.005]). The changes in BMD with time at all 3 measurement sites were significantly different between the treatment groups (P < 0.0001). Changes in radiographic signs of joint damage and in disease activity were similar in the 2 groups. Conclusion. The present study provides the first evidence that long-term treatment with an orally administered bisphosphonate overcomes bone loss and increases bone mass when compared with placebo. This finding may have significance with regard to the treatment of patients with RA.     

The Nottingham health profile in rheumatoid arthritis: correlation with other health status measurements and clinical variables

Objective The overall effect of rheumatoid arthritis (RA) on general health status has drawn attention in recent years. The aim of this study was to determine the clinical relevance of the Nottingham Health Profile (NHP) in RA patients and the relationship between conventional clinical measures, the Health Assessment Questionnaire (HAQ), and the Beck Depression Inventory (BDI)Method One hundred RA patients (mean age 48.9±12.1 years, mean disease duration 101.3±85.5 months) were included in the study. Quality of life, health status, and psychological mood of the patients were assessed using NHP, HAQ, and BDI. The Ritchie Articular Index (RAI), visual analog scale, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor, and modified Larsen Scale were used to assess clinical, laboratory, and radiological changes.Results All subgroups of the NHP significantly correlated to VAS, RAI, BDI, and HAQ scores (P<0.001). Except in the social isolation subgroup, there were significant correlations with ESR (P<0.05, P<0.001, and P<0.0001, respectively). There were no correlations between CRP levels and health status measures (P>0.05).Conclusion The NHP reflects the clinical and psychological status of RA patients and can be used as a sensitive health status measure for clinical evaluation.